CN103261157A - Strigolactam derivatives and their use as plant growth regulators - Google Patents

Strigolactam derivatives and their use as plant growth regulators Download PDF

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CN103261157A
CN103261157A CN2011800600166A CN201180060016A CN103261157A CN 103261157 A CN103261157 A CN 103261157A CN 2011800600166 A CN2011800600166 A CN 2011800600166A CN 201180060016 A CN201180060016 A CN 201180060016A CN 103261157 A CN103261157 A CN 103261157A
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hydrogen
alkyl
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alkylamine
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CN103261157B (en
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M·D·拉契亚
A·德麦斯马伊克
H·C·沃尔夫
P·J·M·容
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Syngenta Participations AG
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • A01N43/38—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/58—[b]- or [c]-condensed
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/94—[b, c]- or [b, d]-condensed containing carbocyclic rings other than six-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Environmental Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Plant Pathology (AREA)
  • Pest Control & Pesticides (AREA)
  • Health & Medical Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pretreatment Of Seeds And Plants (AREA)
  • Indole Compounds (AREA)
  • Cultivation Of Plants (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention relates to novel strigolactam derivatives of formula (I) to processes and intermediates for preparing them, to plant growth regulator compositions comprising them and to methods of using them for controlling the growth of plants and/or promoting the germination of seeds.

Description

Strigolactam derivative and as the purposes of plant-growth regulator
The present invention relates to novel strigolactam derivative, relate to method and intermediate for the preparation of them, relate to the plant growth regulator composition that comprises them, and relate to the method that they is used for control plant-growth and/or promotion seed germination.
The witchweed lactone derivatives is the plant hormone with plant growth regulating and seed germination characteristic; They are described in, for example, and at WO2009/138655, WO2010/125065, WO05/077177, WO06/098626 and Annual Review of Phytopathology(" plant pathology annual report ") (2010), among the 48p.93-117.The witchweed lactone derivatives is similar to synthetic analogue GR24, and known sprouting to parasitic weeds (for example Orobanche species) has influence.In the art, determined that the test that the sprouting of Orobanche seed is carried out is a useful test, so that differentiate witchweed lactone analogue (for example, referring to Plant and Cell Physiology(" plant and stechiology ") (2010), 51 (7) p.1095; And Organic﹠amp; Biomolecular Chemistry(" You Ji ﹠amp; Biological molecular chemistry ") (2009), 7 (17), p.3413).
Now found surprisingly that some strigolactam derivative has the characteristic that is similar to the witchweed lactone.
According to the present invention, provide a kind of compound with chemical formula (I)
Figure BDA00003342326200011
Wherein
W is O or S;
R2 and R3 are hydrogen or C1-C3 alkyl independently;
R4 and R5 be independently hydrogen, halogen, nitro, cyano group, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxyl group, hydroxyl ,-OC (O) R9, amine, N-C1-C3 alkylamine or N, N-two-C1-C3 alkylamine;
R9 is hydrogen, C1-C6 alkyl, C1-C6 alkoxyl group or C1-C6 haloalkyl;
R6 and R7 are hydrogen, C1-C3 alkyl, hydroxyl or C1-C3 alkoxyl group independently;
R8 is hydrogen, nitro, cyano group, C1-C6 alkyl or C1-C6 haloalkyl;
R1 is hydrogen, C1-C6 alkoxyl group, hydroxyl, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine, the C1-C6 alkyl that is randomly replaced by one to five R10, C1-C8 alkyl-carbonyl, C1-C8 alkoxy carbonyl, aryl, the aryl by one to five R10 replacement, heteroaryl, the heteroaryl by one to five R10 replacement, heterocyclic radical, the heterocyclic radical by one to five R10 replacement, benzyl or the benzyl that is replaced by one to five R10;
R10 is hydrogen, cyano group, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxyl group, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;
A 1, A 2, A3 and A 4Be C-X or nitrogen independently of one another, wherein each X can be identical or different, and prerequisite is A 1, A 2, A 3And A 4In to be no more than two be nitrogen;
And X be hydrogen, halogen, cyano group, hydroxyl ,-OC (O) R9, C1-C6 alkoxyl group, C1-C6 alkyl, C1-C6 haloalkyl, C1-C3 hydroxyalkyl, nitro, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine, or NHC (O) R9.
Compound with chemical formula (I) can be with different geometry or optical isomer (diastereomer and enantiomer) or the existence of tautomeric form.This type of all isomer and tautomer and their mixture that is in all proportions have been contained in the present invention, together with the isotropic substance form, and the compound of deuterate for example.The complex compound of all salt, N-oxide compound and the metalloid of the compound with chemical formula (I) has also been contained in the present invention.
Each moieties independent or as the part (for example alkoxyl group, alkoxy carbonyl, alkyl-carbonyl, alkyl amino-carbonyl, dialkylamino carbonyl) of a bigger group be straight chain or side chain, and be for example methyl, ethyl, n-propyl, normal-butyl, n-pentyl, n-hexyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl or neo-pentyl.These alkyl are C preferably 1To C 6Alkyl more preferably is C 1-C 4And most preferably be C 1-C 3Alkyl.
Halogen is fluorine, chlorine, bromine or iodine.
Haloalkyl (independent or as a bigger group, for example part of halogenated alkoxy or halogenated alkylthio) is the alkyl that is replaced by one or more identical or different halogen atoms, and for example is ,-CF 3,-CF 2Cl ,-CH 2CF 3Or-CH 2CHF 2
Hydroxyalkyl is the alkyl that is replaced by one or more hydroxyls, and be for example-CH 2OH ,-CH 2CH 2OH or-CH (OH) CH 3
In the context of the present specification, term " aryl " refers to that one can be the loop systems of monocycle, dicyclo or three rings.The example of this type of ring comprises phenyl, naphthyl, anthryl, indenyl or phenanthryl.A preferred aryl groups is phenyl.
Except as otherwise noted, alkenyl and alkynyl, they are own or as another substituent part, can be straight chain or side chain, and can preferably comprise 2 to 6 carbon atoms, preferably 2 to 4, more preferably be 2 to 3, and suitably the time, can be in ( E)-or ( Z)-configuration.Example comprises vinyl, allyl group and propargyl.
Term " heteroaryl " refers to an aromatic ring system, and this aromatic ring system comprises at least one heteroatoms and is made up of a monocycle or two or more condensed ring.Preferably, monocycle comprises up to three heteroatomss and bicyclic system and comprises that these heteroatomss preferably are selected from nitrogen, oxygen and sulphur up to four heteroatomss.This type of examples of groups comprises pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, furyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazole base, thiazolyl, isothiazolyl, thiadiazolyl group, pyrryl, pyrazolyl, imidazolyl, triazolyl and tetrazyl.A preferred heteroaryl is pyridine.
Term " heterocyclic radical " is defined as comprising heteroaryl and their the undersaturated analogue of undersaturated or part in addition, for example 4,5,6,7-tetrahydrochysene-benzo thiophenyl, 9H-fluorenyl, 3,4-dihydro-2H-phendioxin, 4-dioxane heptyl, 2,3-dihydro-benzofuryl, piperidyl, 1,3-dioxolanyl, 1,3-dioxacyclohexyl, 4,5-dihydro-isoxazole base, tetrahydrofuran base and morpholinyl.
W, R2, R3, R4, R5, R9, R8, R1, R10, A 1, A 2, A 3, A 4And the preferred value of X such as following listing (with any combination).
W is oxygen preferably.
R2 is hydrogen, methyl or ethyl preferably; Most preferably, R2 is hydrogen.
R3 is hydrogen, methyl or ethyl preferably; Most preferably, R3 is hydrogen.
R4 is hydrogen, hydroxyl, methyl or ethyl preferably; Most preferably, R4 is hydrogen or hydroxyl.
R5 is hydrogen, hydroxyl, methyl or ethyl preferably; Most preferably, R5 is hydrogen or hydroxyl.
R6 is hydrogen, methyl or ethyl preferably; Most preferably, R6 is methyl.
R7 is hydrogen, methyl or ethyl preferably; Most preferably, R7 is hydrogen.
R8 is hydrogen, methyl or ethyl preferably; Most preferably, R8 is hydrogen.
R1 preferably hydrogen, C1-C6 alkoxyl group, by or can't help C1-C6 alkyl that one to five R10 replaces, C1-C8 alkyl-carbonyl, C1-C8 alkoxy carbonyl, aryl, the aryl that is replaced by one to five R10, heteroaryl, the heteroaryl that is replaced by one to five R10, heterocyclic radical, the heterocyclic radical, the benzyl that are replaced by one to five R10 or the benzyl that is replaced by one to five R10; More preferably, R1 be hydrogen, C1-C6 alkoxyl group, by or can't help C1-C6 alkyl, C1-C8 alkyl-carbonyl, C1-C8 alkoxy carbonyl, the benzyl that one to five R10 replaces or the benzyl that is replaced by one to five R10; Most preferably, R1 is hydrogen, methyl, ethyl, phenyl, benzyl, acetate or methoxycarbonyl.
R10 is hydrogen, cyano group, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxyl group, C1-C6 haloalkyl independently; Most preferably, R10 is hydrogen, cyano group, nitro, chlorine, bromine, fluorine, methyl, methoxyl group or trifluoromethyl.
Preferably, A 1Be C-X.
Preferably, A 2Be C-X.
Preferably, A 3Be C-X.
Preferably, A 4Be C-X.
Preferably, X is hydrogen, hydroxyl, halogen, cyano group, methyl, ethyl, n-propyl, methylol, trifluoromethyl or methoxyl group.More preferably, X is hydrogen, hydroxyl, methyl, trifluoromethyl or methoxyl group.Even more preferably, X is hydrogen, methyl, hydroxyl or methoxyl group.Most preferably, X is hydrogen, methyl, hydroxyl or methoxyl group.
In a preferred embodiment, provide a kind of compound with chemical formula (I), wherein
W is O;
R2 and R3 are hydrogen, methyl or ethyl independently;
R4 and R5 are hydrogen, hydroxyl, methyl or ethyl independently;
R6, R7 and R8 are hydrogen, methyl or ethyl independently;
R1 is hydrogen, the C1-C6 alkoxyl group, by or the heterocyclic radical of can't help C1-C6 alkyl that one to five R10 replaces, C1-C8 alkyl-carbonyl, C1-C8 alkoxy carbonyl, aryl, the aryl that is replaced by one to five R10, heteroaryl, the heteroaryl that is replaced by one to five R10, heterocyclic radical, being replaced by one to five R10, benzyl or the benzyl that is replaced by one to five R10;
R10 is hydrogen, cyano group, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxyl group or C1-C6 haloalkyl independently;
A 1, A 2, A 3And A 4Be C-X independently of one another; And
X is hydrogen, hydroxyl, halogen, cyano group, methyl, ethyl, n-propyl, methylol, trifluoromethyl or methoxyl group.
In a preferred embodiment, provide a kind of compound with chemical formula (II)
Figure BDA00003342326200061
Wherein
W is O or S;
R2 and R3 are hydrogen or C1-C3 alkyl independently;
R4 and R5 be independently hydrogen, halogen, nitro, cyano group, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxyl group, hydroxyl ,-OC (O) R9, amine, N-C1-C3 alkylamine or N, N-two-C1-C3 alkylamine;
R8 is hydrogen, nitro, cyano group, C1-C6 alkyl or C1-C6 haloalkyl;
R1 is hydrogen, C1-C6 alkoxyl group, hydroxyl, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine, the C1-C6 alkyl that is randomly replaced by one to five R10, C1-C8 alkyl-carbonyl, C1-C8 alkoxy carbonyl, aryl, the aryl by one to five R10 replacement, heteroaryl, the heteroaryl by one to five R10 replacement, heterocyclic radical, the heterocyclic radical by one to five R10 replacement, benzyl or the benzyl that is replaced by one to five R10;
R10 is hydrogen, cyano group, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxyl group, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;
A 1, A 2, A 3And A 4Be C-X or nitrogen independently of one another, wherein each X can be identical or different, and prerequisite is A 1, A 2, A 3And A 4In to be no more than two be nitrogen;
And X be hydrogen, halogen, cyano group, hydroxyl ,-OC (O) R9, C1-C6 alkoxyl group, C1-C6 alkyl, C1-C6 haloalkyl, C1-C3 hydroxyalkyl, nitro, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine or NHC (O) R9;
Perhaps its salt or N-oxide compound.
For A 1, A 2, A 3, A 4, R1, R2, R3, R4, R5, R8 and W preference be identical with the listed preference of corresponding substituting group for these compounds with chemical formula (I).Compound with chemical formula (II) is an intermediate in the compound with chemical formula (I) synthetic.
Following table 1 to 2 comprises examples for compounds of the present invention.
Table 1
Figure BDA00003342326200071
Figure BDA00003342326200081
Figure BDA00003342326200091
Table 2
Figure BDA00003342326200092
Figure BDA00003342326200101
Figure BDA00003342326200111
Compound with chemical formula (I) according to the present invention can self be used as plant-growth regulator or seed germination promotor, but they use preparation adjuvant (for example carrier, solvent and tensio-active agent (SFAs)) to be formulated as plant growth regulating usually or seed germination promotes composition.Therefore, the present invention further provides a kind of plant growth regulator composition, comprised acceptable preparation adjuvant on a kind of plant growth regulating compound with chemical formula (I) and a kind of agricultural.The present invention further provides a kind of plant growth regulator composition, formed by acceptable preparation adjuvant on a kind of plant growth regulating compound with chemical formula (I) and a kind of agricultural in essence.The present invention further provides a kind of plant growth regulator composition, formed by acceptable preparation adjuvant on a kind of plant growth regulating compound with chemical formula (I) and a kind of agricultural.The present invention further provides a kind of seed germination enhancer compositions, comprised acceptable preparation adjuvant on a kind of seed germination promoter compound with chemical formula (I) and a kind of agricultural.The present invention further provides a kind of seed germination enhancer compositions, formed by acceptable preparation adjuvant on a kind of seed germination promoter compound with chemical formula (I) and a kind of agricultural in essence.The present invention further provides a kind of seed germination enhancer compositions, formed by acceptable preparation adjuvant on a kind of seed germination promoter compound with chemical formula (I) and a kind of agricultural.Said composition can exist with the form of the enriched material of dilution before using, though can also make the i.e. composition of usefulness.Usually water finally dilutes, but can replace water, perhaps except water, can also use for example liquid fertilizer, micro-nutrients, biological organism, oil or solvent.
Said composition generally includes by weight from 0.1% to 99%, especially by weight from 0.1% to 95% the compound with Formula I and a kind of preparation adjuvant of from 1% to 99.9% by weight, this preparation adjuvant preferably includes a kind of surfactant of from 0 to 25% by weight.
These compositions can be selected from multiple preparation type; wherein much from Manual on Development and Use of FAO Specifications for Plant Protection Products(" about the development of the FAO standard of plant protection products and the handbook of use); the 5th edition, learn in 1999.But these comprise dust formation pulvis (DP), soluble powder (SP), water-soluble particle (SG), water dispersible granules (WG), wettable powder (WP), particle (GR) (slowly-releasing or release soon), soluble enriched material (SL), oil miscible liquid (OL), ultralow volume of liquid (UL), emulsifiable concentrate (EC), dispersible enriched material (DC), emulsion (oil-in-water (EW) and water-in-oil (EO) both), microemulsion (ME), suspending concentrate (SC), aerosol, capsule suspension liquid (CS) and seed treatment preparation.Under any circumstance, selected preparation type physics, the chemistry and biology characteristic that will depend on the specific purposes of planning and have the compound of chemical formula (I).
But a kind of compound that dust formation pulvis (DP) can be by will having chemical formula (I) and one or more solid diluents (for example, natural clay, kaolin, pyrophyllite, wilkinite, aluminum oxide, montmorillonite, diatomite (kieselguhr), chalk soil, diatomite (diatomaceous earths), calcium phosphate, calcium carbonate and magnesiumcarbonate, sulphur, lime, flour, talcum and other organic and inorganic solid carriers) mix and this mixture mechanically are milled into fine powder and prepare.
A kind of compound and one or more water-soluble inorganic salts (for example sodium bicarbonate, yellow soda ash or sal epsom) that soluble powder (SP) can be by will having chemical formula (I) or the mixture of one or more water-soluble organic solids (for example polysaccharide) and one or more wetting agents randomly, one or more dispersion agents or described dose mix to prepare to improve water dispersible/water-soluble.Then this mixture is ground to form fine powder.Also can be with the similar compositions granulating to form water-soluble granular (SG).
Wettable powder (WP) can be by will having chemical formula (I) a kind of compound and one or more solid diluents or carrier, one or more wetting agents and preferably, one or more dispersion agents, and randomly, one or more suspension agent mixes to prepare to promote the dispersion in liquid.Then this mixture is ground to form fine powder.Also can be with the similar compositions granulating to form water-dispersible granular material (WG).
Can form granule (GR) like this: a kind of compound by will having chemical formula (I) and the mixture pelleting of one or more powdery solid diluent or carriers form, perhaps a kind of compound (or its solution in a kind of suitable agent) by will having chemical formula (I) absorbs honeycombed grain material (float stone for example, attapulgite clay, Fuller's earth, diatomite (kieselguhr), diatomite (diatomaceous earths) or corn cob meal), it is (for example husky perhaps to be adsorbed onto hard core material by a kind of compound (or its solution in being fit to agent) that will have chemical formula (I), silicate, mineral carbonic acid salt, vitriol or phosphoric acid salt) go up and if necessary, carry out the preformed blank particle of dry cause and form.Generally comprise solvent (for example aliphatics and aromatic petroleum solvent, alcohol, ether, ketone and ester) and tackiness agent (for example polyvinyl acetate, polyvinyl alcohol, dextrin, sugar and vegetables oil) with the agent of helping to absorb or adsorb.Can also in particle, comprise one or more other additives (for example emulsifying agent, wetting agent or dispersion agent).
Dispersible enriched material (DC) can be by a kind of compound that will have chemical formula (I) prepares in the water-soluble or organic solvent (for example ketone, alcohol or glycol ether).These solution can contain tensio-active agent (for example being used for improving water-dilutable or prevent crystallization in spray cistern).
Emulsifiable concentrate (EC) or O/w emulsion (EW) can be dissolved in by a kind of compound that will have chemical formula (I) in a kind of organic solvent (mixture that randomly comprises one or more wetting agents, one or more emulsifying agents or described dose) and preparing.The organic solvent that is fit to that uses in EC comprises aromatic hydrocarbon (for example alkylbenzene or alkylnaphthalene, for example SOLVESSO100, SOLVESSO150 and SOLVESSO200; SOLVESSO is registered trademark), the dimethylformamide of ketone (for example pimelinketone or methylcyclohexanone) and alcohol (for example phenylcarbinol, furfuryl alcohol or butanols), N-alkyl pyrrolidone (for example N-Methyl pyrrolidone or N-octylpyrrolidone), lipid acid (C for example 8-C 10The lipid acid dimethylformamide) and hydrochloric ether.Spontaneously emulsification when the EC product can be in adding water produces and has enough stability in order to allow emulsion by suitable equipment spray application.
The preparation of EW relate to acquisition as a kind of liquid (if it at room temperature is not liquid, then it can be melted under the reasonable temperature that typically is lower than 70 ° of C) or be in the compound with chemical formula (I) of (by it being dissolved in suitable solvent) in the solution, under high-shear, gained liquid or emulsifying soln are advanced to comprise in the water of one or more SFA then, to produce emulsion.The solvent that is fit to that uses in EW comprises that vegetables oil, hydrochloric ether (for example chlorobenzene), aromatic solvent (for example alkylbenzene or alkylnaphthalene) and other have the suitable organic solvent of low solubility in water.
Microemulsion (ME) can be by the adulterant of water with one or more solvents and one or more SFA mixed to prepare, spontaneously to produce a kind of thermodynamically stable isotropic liquid formulations.A kind of compound with chemical formula (I) be present in the water at the very start or solvent/SFA adulterant in.The solvent that is applicable to ME comprises that the above is used for EC or EW those.ME can be oil-in-water system or water-in-oil system (existing which kind of system to test to measure by conductivity) and can be suitable for mixing water miscible and oil-soluble pesticides in same preparation.ME is suitable for dilution and enters in the water, remains microemulsion or forms conventional O/w emulsion.
Suspensoid enriched material (SC) can comprise water-based or the non-aqueous suspension of the finely divided insoluble solids particle of the compound with chemical formula (I).SC can randomly use one or more dispersion agents to have the solid chemical compound of chemical formula (I) to prepare by ball milling or pearl grinding tool in being fit to medium, to produce the fine particle suspension of this compound.In said composition, can comprise one or more wetting agents, and can comprise that suspension agent is to reduce the settling velocity of particle.Alternately, can be with having a kind of compound dry grinding of chemical formula (I) and it being added in the water that comprises the above agent, to produce the finished product of wishing.
The aerosol preparation comprises have chemical formula a kind of compound of (I) and the propelling agent (for example, normal butane) that is fit to.Also a kind of compound with chemical formula (I) can be dissolved in or be scattered in the suitable medium (for example water or liquid that can be miscible with water, for example n-propyl alcohol) to be provided at the composition that uses in non-pressurized hand spray pump.
Capsule suspension liquid (CS) can be by to prepare with preparation EW preparation similar mode, except additional polymerization procedure, make to obtain the water dispersion of oil droplet, wherein each oil droplet is aggregated beyond the region of objective existence shell parcel and contains the have chemical formula compound of (I) and corresponding optional carrier or thinner.This polymer shell can prepare by the interfacial polycondensation reaction or by coacervation.These compositions can provide the controlled release of the compound with chemical formula (I) and them can be used for seed treatment.Compound with chemical formula (I) also can be formulated in the biodegradable polymer matrix, so that the controlled release slowly of this compound to be provided.
Said composition can comprise that one or more additives (for example pass through to improve lip-deep wettability, reservation or distribution with the biology quality of improving said composition; Rain proofness on surface treated; Absorption or transport property with compound of chemical formula (I)).Such additive comprises tensio-active agent (SFAs), based on the spray additives of oil, for example some mineral oil or crude vegetal (for example soybean and rapeseed oil), and these and other biological strengthen the adulterant of adjuvant (can help or modification has the composition of effect of the compound of chemical formula (I)).
Wetting agent, dispersion agent and emulsifying agent can be positively charged ion, negatively charged ion, SFA both sexes or nonionic type.
The cationic SFA that is fit to comprises quaternary ammonium compounds (for example cetyl trimethylammonium bromide), tetrahydroglyoxaline and amine salt.
The anionic SFA that is fit to comprises an alkali metal salt of lipid acid, analiphatic sulphur acid monoester class salt (as Sulfuric acid,monododecyl ester, sodium salt), the salt of sulfonated aromatic compounds of group is (as Sodium dodecylbenzene sulfonate, calcium dodecylbenzene sulphonate, butyl naphthalene sulfonate and two-sec.-propyl-and the mixture of three-sec.-propyl-sodium naphthalene sulfonate), the sulfuric acid ethers, alcohol sulfate ethers (as laureth-3-sodium sulfate), carboxylic acid ethers (as laureth-3-carboxylic acid sodium), phosphoric acid ester (from one or more Fatty Alcohol(C12-C14 and C12-C18) and phosphoric acid (mainly being monoesters) or and Vanadium Pentoxide in FLAKES (mainly being diester) between, the product of the reaction between lauryl alcohol and four phosphoric acid for example; These products can be by ethoxylation in addition), sulfo-succinamate, paraffin or alkene sulfonate, tauride and ligninsulfonate.
The SFA that is fit to of amphoteric type comprises trimethyl-glycine, propionic salt and glycinate.
The SFA of the nonionic type that is fit to comprise oxirane (for example oxyethane, propylene oxide, butylene oxide ring or its mixture) and Fatty Alcohol(C12-C14 and C12-C18) (for example oil base alcohol or hexadecanol) or with the condensation product of alkylphenol (for example octyl phenol, nonyl phenol or octyl cresol); The partial ester of derivation of self-long chain lipid acid or hexitan; The condensation product of described partial ester and oxyethane; Block polymer (containing oxyethane and propylene oxide); Alkanolamine; Monoesters (as fatty acid polyglycol ester); Amine oxide (as lauryl dimethyl amine oxide); And Yelkin TTS.
The suspension agent that is fit to comprises hydrophilic colloid (for example polyose, polyvinylpyrrolidone or Xylo-Mucine) and expanded clay (as wilkinite or attapulgite).
It is a kind of for the method a place coordinate plant growth that the present invention still further provides, wherein, this method comprise use to this place a kind of plant growth regulating amount according to composition of the present invention.
It is a kind of for the method that promotes seed germination that the present invention also provides, comprise use to these seeds or the place that comprises seed a kind of promote the seed germination amount according to composition of the present invention.
Usually use by spraying said composition, typically by being used for large-area tractor mounted spraying machine, but can also use additive method, for example dusting (for powder), drip or soak.Alternately, said composition can in ditch dug with a plow, use or before plantation or plantation the time be applied directly on the seed.
Of the present invention have on the compound of chemical formula (I) or a part that composition can be applied to plant, plant, plant organ, the plant propagation material or in its peripheral region.
In one embodiment, the present invention relates to a kind of method for the treatment of of plant propagation material, comprise promoting the significant quantity of sprouting and/or coordinate plant growth to be administered on the plant propagation material with one composition of the present invention.The invention still further relates to a kind of the have compound of chemical formula (I) or the plant propagation material of compositions-treated of the present invention.Preferably, this plant propagation material is seed.
Term " plant propagation material " refers to all reproduction parts of plant, seed for example, and they can be used for the latter's propagation, and vegetative vegetable material, for example transplant a cutting and stem tuber.Particularly, can mention seed, root, fruit, stem tuber, bulb and root (shape) stem here.
The method that activeconstituents is administered on the plant propagation material (especially seed) is known in this area, and comprises soaking of reproductive material deposited (dressing), coating, granulation and dipping application process.This processing can be between seed results and planting seed any time or in the sowing process, be administered on this seed.This seed can also apply before or after this processing.This compound with chemical formula (I) can randomly be used with a kind of coating or process combination of controlled release, so that this compound discharges in time.
Composition of the present invention can be before seedling or postemergence application.Suitable, when said composition is used to regulate the crop plants growth, can be before seedling or postemergence application, but preferably at the postemergence application of crop.When said composition is used to promote seed germination, can preemergence application.
Rate of application with compound of Formula I can change and depend on that the character of soil, application process are (before the seedling or behind the seedling in broad range; Seed dressing; Be applied to the seed ditch dug with a plow; No-tillage use etc.), crop plants, prevailing weather conditions and by other factors, time of application and the target crop of application process domination.Be used for leaf or soak when using, the compound with Formula I according to the present invention is particularly used from the ratio of 5g/ha to 1000g/ha usually with from 1g/ha to 2000g/ha.When being used for seed treatment, this rate of application is normally between every 100kg seed 0.0005g and 150g.
Can comprise with plant therein according to composition of the present invention: crop such as cereal (for example wheat, barley, rye or oat); Beet (for example sugar beet or fodder beet); Fruit (for example the operatic circle, drupe or berry, for example apple, pears, plum, peach, almond, cherry, strawberry, raspberry or blackberry, blueberry); Leguminous plants (for example broad bean, shore beans, pea or soybean); Oilseed plant (for example rape, leaf mustard, opium poppy, olive, Sunflower Receptacle, coconut, Viscotrol C plant, cocoa beans or Semen arachidis hypogaeae); Mellon plant (for example marrow, cucumber or muskmelon); Textile plant (for example cotton, flax, hemp or jute); Citrus fruit (for example orange, lemon, natsudaidai or orange); Vegetables (for example spinach, lettuce, asparagus, Caulis et Folium Brassicae capitatae, Radix Dauci Sativae, onion, tomato, potato, cucurbit or red pepper); Lauraceae (for example avocado, Chinese cassia tree or camphor); Corn; Paddy rice; Tobacco; Nut; Coffee; Sugarcane; Tea; Vine; Hops; Durian; Banana; The natural rubber plant; Turf or ornamental plant (for example flowers, shrub, deciduous tree or evergreen plant for example softwood tree).This inventory does not represent any restriction.
The present invention also can be used for regulating growth, or promotes the seed germination of non-crop plants, for example, helps control weeds by synchronous sprouting.
The crop that is to be understood that comprises that also those are by the breeding method of routine or the crop that passes through the genetically engineered modification.For example, the present invention can be used in combination with those crops that has been endowed the tolerance of the weedicide (for example ALS-, GS-, EPSPS-, PPO-, ACC enzyme and HPPD inhibitor) to weedicide or plurality of classes.Having given its example to the crop of the tolerance of imidazolone (for example, imazamox) by the breeding method of routine is
Figure BDA00003342326200181
Rape in summer (Corolla).The example that has been endowed the crop of the tolerance of multiple weedicide by genetic engineering method comprises glyphosate and careless fourth phosphine resistance corn variety, and these corn varieties exist
Figure BDA00003342326200182
With
Figure BDA00003342326200183
Be commercially available under the trade name.Giving crop plants is known to the method for the tolerance of HPPD inhibitor, for example from WO0246387; For example crop plants is genetically modified about a kind of polynucleotide, comprise a coding derived from a kind of bacterium (more particularly, from Pseudomonas fluorescens or Shiva Salmonella (Shewanella colwelliana),) or from plant (more particularly, derived from monocotyledons or still more particularly, from barley, corn, wheat, paddy rice, Brachiaria, Chenchrus, lolium, festuca, setaria, yard grass genus, sorghum or Avena species) the dna sequence dna of HPPD enzyme of HPPD inhibitor resistance.
Crop will also be understood that to being to be endowed those of the resistance of harmful insect by genetic engineering method, for example Bt corn (anti-European corn borer), Bt cotton (anti-cotton anthonomus grandis) and also have Bt potato (anti-Colorado beetle).The example of Bt corn is
Figure BDA00003342326200191
Bt176 corn hybridization body (just reaching earlier seeds company).This Bt toxin is a kind of protein that is formed naturally by the bacillus thuringiensis soil bacteria.Toxin maybe can synthesize the case description of transgenic plant of this toxoid in for example EP-A-451878, EP-A-374753, WO93/07278, WO95/34656, WO03/052073 and EP-A-427529.Comprise that one or more coding insecticide resistances and the example of the transgenic plant of the gene of expressing one or more toxin are
Figure BDA00003342326200192
(corn),
Figure BDA00003342326200193
(corn),
Figure BDA00003342326200194
(cotton),
Figure BDA00003342326200195
(cotton),
Figure BDA00003342326200196
(potato),
Figure BDA00003342326200197
With
Figure BDA00003342326200198
Its plant crop or seed material all can be antiweed and be anti-insect ingest (" stack " transgene result) simultaneously.For example, seed can be glyphosate tolerant having the insecticidal Cry3 albumen ability of expression simultaneously.
Crop will also be understood that to be to comprise that breeding by routine or engineered method obtain and comprise so-called output type (output) proterties (for example improved storage power, higher nutritive value and improved fragrance).
These compounds of the present invention can be made by the following method.
Scheme 1-selects A
Figure BDA00003342326200199
I) in the presence of the catalyzer/Fas lignand system (normally a kind of palladium (0) complex compound) that is fit to, have the compound (wherein R is C1 to C6 alkyl) of chemical formula (XIV) can be by having chemical formula (XIII) with a kind of allyl deriv (wherein Z is boron or tin derivative) processing with chemical formula ZC (R4R5) C (R3) CH2 compound (wherein X is that Br or I and R are C1 to C6 alkyl) and make.Compound (wherein X is that Br or I and R are C1 to C6 alkyl) with chemical formula (XIII) is compound known or can be by the method known to those skilled in the art manufacturing.
The compound that ii) has chemical formula (XV) can have chemical formula the compound (wherein R is C1 to C6 alkyl) of (XIV) is made by handling with a kind of alkali (for example sodium hydroxide or lithium hydroxide) hydrolysis ester group.
Scheme 1-selects B
Figure BDA00003342326200201
I) having the compound (wherein X is Br or I) of chemical formula (XII) can be by having a chemical formula HNR ' with a kind of 2(wherein R ' is not chirality, for example sec.-propyl or R ' 2Be chirality, for example the amine of (R, R)-2,5-dimethyl pyrrolidine) is handled the compound (wherein R is H, C1-C6 alkoxyl group, Cl, F or Br) with chemical formula (XIII) and is made.When R is H, this type of reaction can be at coupling agent (DCC(N for example, N '-dicyclohexylcarbodiimide), EDC(1-ethyl-3-[3-dimethylamino-propyl group] carbodiimide hydrochloride) or two (2-oxo-3-oxazolidinyl) phosphonyl chlorides of BOP-Cl()) exist down, in the presence of alkali (for example pyridine, triethylamine, 4-(dimethylamino) pyridine or diisopropylethylamine), and randomly in the presence of nucleophilicity catalyzer (for example hydroxybenzotriazole or 1-hydroxyl-7-azepine benzotriazole), carry out.When R was Cl, this type of reaction can for example, in the presence of pyridine, triethylamine, 4-(dimethylamino) pyridine or diisopropylethylamine, and optionally be carried out in the presence of the nucleophilicity catalyzer under alkaline condition.Alternately, this reaction can be carried out in a biphasic system (comprising a kind of organic solvent, ethyl acetate, and a kind of water solvent, the solution of preferred a kind of sodium bicarbonate).When R is the C1-C6 alkoxyl group, can be by in a thermal process, ester and amine being heated together and ester being converted into acid amides.Have the compound of chemical formula (XIII) and have chemical formula R ' 2The amine of NH is compound known or can prepares by method known to those skilled in the art.
Ii) in the presence of the catalyzer/Fas lignand system (normally a kind of palladium (0) complex compound) that is fit to, (wherein R ' is not chirality, for example sec.-propyl or R ' to have the compound of chemical formula (XI) 2It is chirality, (R for example, R)-2,5-dimethyl pyrrolidine) can make by handling the compound (wherein X is Br or I) with chemical formula (XII) with a kind of allyl deriv (wherein Z is boron or tin derivative) with chemical formula ZC (R4R5) C (R3) CH2.
Iii) alternately, having the compound of chemical formula (XI) can be from compound (wherein R is the compound that H(has chemical formula (XV)), C1-C6 alkoxyl group, Cl, F or the Br with chemical formula (XIV)) as at i) describe prepare.
Scheme 2-selects A
Figure BDA00003342326200211
Compound with chemical formula (X) can be by handle the have chemical formula compound of (XV) with a kind of reagent for the synthesis of acyl chlorides (for example (1-chloro-2-methyl-propenyl)-dimethyl-amine), subsequently by making with the reaction of a kind of alkali (for example triethylamine).The formation of acyl chlorides is known and can realize with multiple other reagent (for example thionyl chloride, oxalyl chloride (Oxalyl chloride) or phosphorus trichloride) for those skilled in the art.Second reaction is for known to those skilled in the art, and this reaction is by handling via a kind of intramolecular ketene cycloaddition.
Scheme 2-selects B
Figure BDA00003342326200221
In the presence of a kind of alkali (for example trimethylpyridine), compound with chemical formula (X) can be by handling the have chemical formula compound of (XI) to provide a kind of ketene imido intermediate with a kind of dewatering agent (for example trifluoromethanesulfanhydride anhydride), via the intramolecularly cycloaddition, be hydrolyzed to make by water subsequently.Use has the compound (R ' wherein of chemical formula (XI) 2Be chirality) provided the chipal compounds with chemical formula (X), (IX), (VIII), (VII), (VI), (IV), (III), (II), (I).
Scheme 3
Figure BDA00003342326200222
Compound with chemical formula (IX) can have chemical formula the compound of (X) is made by handling with a kind of peroxide derivative (for example hydrogen peroxide).In the Bayer-Villiger oxidation (Baeyer-Villiger oxidation) that is used for carbonyl compound is converted into lactone or ester under one's name, this reaction is for well-known to those having ordinary skill in the art.
Scheme 4
Figure BDA00003342326200231
I) have the compound (wherein W is oxygen) of chemical formula (VII) can be via the compound with chemical formula (VIII) (wherein R2 is that hydrogen and W are oxygen) from compound with chemical formula (IX) by following preparation: a kind of solvent (for example water), handle with a kind of oxyhydroxide (for example sodium hydroxide) of alkali and be hydrolyzed into acid, subsequently, in the presence of sodium metaperiodate, carry out in-situ oxidation by handling with a kind of oxygenant (for example ruthenium chloride).Compound (for example indeneacetic acid, 1-hydroxyl-gamma lactone) with chemical formula (IX) be commercially available or as above 4) described in prepare.
Ii) in the presence of a kind of acid (for example sulfuric acid in methyl alcohol or ethanol), the compound (wherein R is that C1-C6 alkyl and W are oxygen) with chemical formula (VI) can prepare by the esterification of handling with a kind of alcohol from having the compound of chemical formula (VII).Alternately, the compound with chemical formula (VI) can be from the parent material of commercialization, and for example indone derivative preparation is described in these derivatives such as the document (referring to for example: Bioorganic﹠amp; Medicinal Chemistry(" biological You Ji ﹠amp; Pharmaceutical chemistry ") (2008), 16 (8), 4438; Journal of the Chemical Society, Perkin Transactions1:Organic and Bio-Organic Chemistry(" Chemical Society's magazine, the pul gold can report 1: organic and bioorganic chemistry ") (1999), (18), 2617; WO2005097093; Monatshefte fuer Chemie (1986), 117 (5), 621).
Scheme 5
Figure BDA00003342326200241
I) have chemical formula (III) compound can (wherein R be hydrogen from compound with chemical formula (VI), be methyl or ethyl as R for example), via by the amine (for example methylamine) of replacement and the reduction amination effect of the reaction of a kind of reductive agent (for example sodium cyanoborohydride), prepare by the original position intramolecular cyclization subsequently.
Ii) alternately, compound with chemical formula (IIIa) can be from the compound (wherein R is H) with chemical formula (VI), via by the reduction amination effect of amine (for example ammonium acetate) with the reaction of a kind of reductive agent (for example sodium cyanoborohydride), prepare by the original position intramolecular cyclization subsequently.
Iii) alternately, the compound with chemical formula (IIIa) can via using a kind of hydroxylammonium salt and a kind of alkali (for example sodium acetate or pyridine) to form oxime, pass through to use and H subsequently from having the compound of chemical formula (VI) 2Carry out hydrogenization with a kind of catalyzer (for example Pd/C or Raney nickel), or other known methods (for example zinc in acetic acid) reduction intermediate oxime prepares.
In the presence of a kind of alkali (for example sodium hydride), the compound (wherein R1 is not hydrogen) with chemical formula (III) can prepare from compound (wherein R1 is H) with chemical formula (IIIa) alkylated reaction via the reaction by acid amides and a kind of alkylating agent (for example haloalkane).
At a kind of alkali (for example potassiumphosphate) and a kind of suitable catalyzer (normally copper (I) salt) and a kind of part (dimethyl ethane-1 for example, the 2-diamines) under the existence, compound (wherein R1 is the group of an aromatic or heteroaromatic) with chemical formula (III) can prepare by acid amides and the reaction with aromatic or heteroaromatic compound (X is a kind of halogen) of chemical formula ArX from the compound (wherein R1 is H) with chemical formula (IIIa).
At a kind of coupling agent (DCC(N for example; the N'-dicyclohexylcarbodiimide); EDC(1-ethyl-3-[3-dimethylamino-propyl group] carbodiimide hydrochloride) or two (2-oxo-3-oxazolidinyl) phosphonium chlorides of BOP-Cl()) exist down; at a kind of alkali (pyridine for example; triethylamine; 4-(dimethylamino) pyridine or diisopropylethylamine) exist down; and randomly in the presence of a kind of nucleophilic catalyst (for example hydroxybenzotriazole), the compound (wherein R1 is carbonyl derivative) with chemical formula (III) can prepare by the compound with chemical formula (IIIa) and the acylation reaction with compound (wherein R is OH) of chemical formula V.Randomly, when R was Cl or OC (O) C1-C6 alkoxyl group, acylation reaction can randomly be carried out in the presence of the nucleophilicity catalyzer under alkaline condition (for example, in the presence of pyridine, triethylamine, 4-(dimethylamino) pyridine or diisopropylethylamine).Alternately, this reaction can be carried out in a biphasic system (comprising a kind of organic solvent, ethyl acetate, and a kind of water solvent, the solution of preferred a kind of sodium bicarbonate).Randomly, when R be C 1-C 6During alkoxyl group, this acid amides can be by heating ester (V) and acid amides (IIIa) prepares together.R ' can be alkyl or alkoxyl group.In addition, have chemical formula (III) compound can as at Journal of Pharmaceutical Sciences(" pharmaceutical science magazine ") 1973Vol.62, No.8, p1363, Journal of Organic Chemistry(" organic chemistry magazine ") (1994), 59 (2), 284, Russian Journal of Organic Chemistry(" Russia's organic chemistry magazine "), Vol.41, No.3, the preparation of getting off of racemic form described in 2005, pp.361 or the WO84/00962.
Compound (A wherein with chemical formula (III) 1, A 2, A 3And A 4Be C-CN independently) can use palladium catalyst (for example tetra-triphenylphosphine palladium) and cyanide salt (for example zinc cyanide) from compound with chemical formula (III) (A wherein 1, A 2, A 3And A 4Be that C-X(X is a kind of halogen independently)) prepare.
In the presence of sulfuric acid, has the compound (A wherein of chemical formula (III) 1, A 2, A 3And A 4Be C-NO independently 2) can be by using nitric acid for example nitrification from compound with chemical formula (III) (A wherein 1, A 2, A 3And A 4Be C-H independently) prepare.
In the presence of the catalyzer/Fas lignand system (normally a kind of palladium (0) complex compound) that is fit to, has the compound (A wherein of chemical formula (III) 1, A 2, A 3And A 4Be C-allyl group or substituted C-allyl group independently) compound by having chemical formula (III) (A wherein 1, A 2, A 3And A 4Be that C-X(X is leavings group, for example a halogen independently)) prepare with the reaction of allyl group boron or allyl group tin derivative.These reactions are reined in (Stille) coupling and Su Chuji (Suzuki) coupling as the history Supreme Being accordingly, be for known to those skilled in the art, referring to for example: Strategic Applications of Named Reactions in Organic Synthesis(" the strategic application of name reaction in the organic synthesis "); Kurti, Laszlo(Ku Erdilaziluo); Czako, Barbara(Cao Ke Barbara); The editor. U.S. .(2005), press: love to think only your academic press, the Massachusetts, Burlinton .448 page or leaf (Su Chuji coupling) and p438(history Supreme Being rein in coupling) and the reference quoted.
Compound (A wherein with chemical formula (III) 1, A 2, A 3And A 4Being as described for the compound with chemical formula (I)) hydrogenation catalyst (for example palladium charcoal) that can be by using a kind of standard is to compound with chemical formula (III) (A wherein 1, A 2, A 3And A 4Be the C-allyl deriv independently) hydrogenization prepare.
Compound (wherein R4 or R5 are not hydrogen) with chemical formula (III) can use a kind of oxygenant (for example potassium permanganate or chromic oxide) to prepare to provide ketone (R4=R5=O) via the oxidation of benzyl position from the compound (wherein R4 and R5 are H) with chemical formula (IIIa).Compound (III) (wherein R4=OH and R5=H) can be gone back original preparation by using a kind of reductive agent (for example sodium borohydride) to this ketone from corresponding ketone.Alternately, in the presence of p-toluol sulfonamide and iodine, the compound (wherein R4=OAc and R5=H) with chemical formula (III) can directly prepare by carrying out oxidation with iodobenzene diacetate.
Compound (III) (wherein R4=F and R5=H) can from compound (III) (wherein R4=OH and R5=H) by with a kind of fluorizating agent (for example diethylaminosulfur trifluoride or Deoxo-Fluor TM) react to prepare.
Scheme 6
Figure BDA00003342326200271
Compound with chemical formula (II) can prepare via the reaction with carbamate derivatives (for example methyl-formiate) from the compound with chemical formula (III) in the presence of a kind of alkali (for example diisopropylamino lithium or potassium tert.-butoxide).Alternately, the compound with chemical formula (II) can prepare via the hydrolytic action with a kind of acid (for example hydrogenchloride) from the compound with chemical formula (IV).Compound with chemical formula (IV) can prepare via the reaction with Bu Leide Neck reagent (Bredereck's reagent) (two (dimethylamino) methane of tert.-butoxy) (wherein R is methyl or analogue) from the compound with chemical formula (III).
Compound (A wherein with chemical formula (II) 1, A 2, A 3And A 4Being as described for the compound with chemical formula (I)) hydrogenation catalyst (for example palladium charcoal) that can be by using a kind of standard is to compound with chemical formula (II) (A wherein 1, A 2, A 3And A 4Be the C-allyl deriv independently) hydrogenization prepare.
Compound (wherein R1 is carbonyl) with chemical formula (II) can pass through acidylate from the compound (wherein R1 is H) with chemical formula (II), and the selective hydrolysis by this two acylate is used for preparing subsequently.This acylation reaction can be at alkaline condition (for example; in the presence of pyridine, triethylamine, 4-(dimethylamino) pyridine or diisopropylethylamine) under; randomly in the presence of nucleophilicity catalyzer (for example 4-(dimethylamino) pyridine), (wherein X is halogen or OH or (R1) by compound (II) and a kind of compound with chemical formula R1X 2O) reaction is carried out.This hydrolytic action can be carried out in a kind of alcoholic solvent in the presence of a kind of alkali (for example salt of wormwood).
Figure BDA00003342326200281
Compound with chemical formula (IIb) can be from the compound (wherein R is alkyl, for example the tertiary butyl) with chemical formula (IIa), via handling to prepare with a kind of acid (for example trifluoroacetic acid or HCl).
Scheme 7
Figure BDA00003342326200282
Compound with chemical formula (I) can be in the presence of a kind of alkali (for example as potassium tert.-butoxide or Hunig alkali), from having the compound of chemical formula (II), be that the nucleophilic substitution of the 5H-furanone derivatives of a leavings group (for example bromine in the position 5) prepares via having a leavings group (LG) and LG.
Alternately, randomly in the presence of a kind of alkali (for example sodium hydride), has the compound (R wherein of chemical formula (I) 1Be a kind of alkyl derivative or benzyl derivative) can be from compound with chemical formula (Ia) (R wherein 1Be H), prepare via the alkylated reaction of the reaction by amine and a kind of alkylating agent (for example haloalkane, benzyl halide).
Alternately, at a kind of coupling agent (DCC(N for example, N'-dicyclohexyl-carbodiimide), EDC(1-ethyl-3-[3-dimethylamino-propyl group] carbodiimide hydrochloride) or two (2-oxo-3-oxazolidinyl) phosphonium chlorides of BOP-Cl()) exist down, at a kind of alkali (pyridine for example, triethylamine, 4-(dimethylamino) pyridine or diisopropylethylamine) exist down, and randomly in the presence of a kind of nucleophilic catalyst (for example hydroxybenzotriazole), compound with chemical formula (I), one of them carbonyl derivative can be from compound with chemical formula (Ia) (R wherein 1Be H), prepare via the acylation reaction with the compound with chemical formula V (wherein R is OH).Randomly, when R was Cl or OC (O) C1-C6 alkoxyl group, this acylation reaction can randomly be carried out in the presence of the nucleophilicity catalyzer under alkaline condition (for example, in the presence of pyridine, triethylamine, 4-(dimethylamino) pyridine or diisopropylethylamine).Alternately, this reaction can be carried out in a biphasic system (comprising a kind of organic solvent, ethyl acetate, and a kind of water solvent, the solution of preferred a kind of sodium bicarbonate).Randomly, when R be C 1-C 6During alkoxyl group, this acid amides can be by heating ester (V) and acid amides (Ia) prepares together.R ' can be alkyl or alkoxyl group.
Compound (wherein, W is sulphur) with chemical formula (I) can prepare by the processing with sulfo-transfering reagent (for example, Lao Weisen reagent or thiophosphoric anhydride) from the compound (wherein, W is oxygen) with chemical formula (I).
Example
The method of following HPLC-MS is used for analyzing these compounds:
Method A: the ZQ mass spectrograph (Waters, the Penelope Milford, the Massachusetts, spectra re-recorded goes up in the U.S. (Waters Corp.Milford, MA, USA)), this mass spectrograph is equipped with electrospray source (ESI; 100 ° of C of source temperature; 250 ° of C of desolvation temperature; Taper hole voltage 30V; Taper hole gas flow 50L/Hr, desolvation gas flow 400L/Hr, mass range: 100Da to 900Da) and an Agilent (Agilent) 1100LC(post: the C18 of Gemini, 3um particle size, 110 dusts, 30x3mm(F door, Tuo Lunsi, California, the U.S. (Phenomenex, Torrance, CA, USA)); Column temperature: 60 ° of C; Flow velocity 1.7mL/min; Elutriant A:H 2O/HCOOH100:0.05; Elutriant B:MeCN/MeOH/HCO 2H80:20:0.04; Gradient: 0min5%B; 2min-2.8min100%B; 2.9min-3min5%B; UV detects: 200nm-500nm, resolving power 2nm.Before MS analyzed, this stream was split rear pillar (split postcolumn).
Method B: go up spectra re-recorded at ZMD mass spectrograph (mass spectrograph, Manchester, Britain (Micromass, Manchester UK)), this mass spectrograph is equipped with electrospray source (ESI; 80 ° of C of source temperature; 200 ° of C of desolvation temperature; Taper hole voltage 30V; Desolvation gas flow 600L/Hr; Mass range: 100Da to 900Da) and an Agilent (Agilent) 1100LC(post: the C18 of Gemini, 3um particle size, 110 dusts, 30x3mm(F door, Tuo Lunsi, California, the U.S. (Phenomenex, Torrance, CA, USA)); Column temperature: 60 ° of C; Flow velocity 1.7mL/min; Elutriant A:H 2O/HCO 2H100:0.05; Elutriant B:MeCN/MeOH/HCO 2H80:20:0.04; Gradient: 0min5%B; 2min-2.8min100%B; 2.9min-3min5%B; UV detects: 200nm-500nm, resolving power 2nm.Before MS analyzed, this stream was split rear pillar (split postcolumn).
Method C: go up spectra re-recorded at API2000/Q-TRAP mass spectrograph (Applied Biosystems, Inc. (Applied Biosystems)), this mass spectrograph is equipped with electrospray source (ESI; 200 ° of C of source temperature; Kapillary 5.5Kv, (removing a bunch voltage 50V), (focus voltage 400V, entrance voltage 10V), (gas curtain gas 30PSI, GS140PSI, GS250PSI), mass range: 100Da to 800Da) and the SIL HTC/UFLC(post of island Tianjin company (Shimadzu): referring to table H); Column temperature: 25 ° of C; Flow velocity 1.2mL/min; Elutriant A: at H 210mM NH among the O 4OAc; Elutriant B:MeCN; Gradient: 0.01min10%B; 1.5min30%B; 3min-4min90%B; 5min10%B; UV detects: 200nm and 260nm,
Before MS analyzed, this stream was split rear pillar (split post column).
Method D: spectra re-recorded on Agilent (Agilent) G1956A mass spectrograph, this mass spectrograph is equipped with electrospray source (ESI; 100 ° of C of source temperature; 350 ° of C of desolvation temperature; Kapillary 4kV; Desolvation gas flow 10L/Hr; Mass range: 100Da to 1000Da) and an Agilent (Agilent) 1100LC(post: Diescovery HS-C18, the 3um particle size, 110 dusts, 50x4.6mm, Supelco569250-U); Column temperature: n.a; Flow velocity 2.20mL/min; Elutriant A:MeCN/TFA100:0.05; Elutriant B:H 2O/TFA100:0.05; Gradient: 0min10%A, 5min90%A, 6min99%A; UV detects: 190nm-400nm, resolving power 2nm.
Method E: the SQD mass spectrograph (Waters, the Penelope Milford, the Massachusetts, spectra re-recorded goes up in the U.S. (Waters Corp.Milford, MA, USA)), this mass spectrograph is equipped with electrospray source (ESI; 150 ° of C of source temperature; 250 ° of C of desolvation temperature; Taper hole voltage 45V; Desolvation gas flow 650L/Hr, mass range: 100 to 900Da) and an Agilent (Agilent) UPLC(post: the C18 of Gemini, 3um, 30x2mm(F door, Tuo Lunsi, California, the U.S. (Phenomenex, Torrance, CA, USA)); The C18 of LC(post: Gemini, the 3um particle size, 110 dusts, 30x3mm(F door, Tuo Lunsi, the California, the U.S. (Phenomenex, Torrance, CA, USA)); Column temperature: 60 ° of C; Flow velocity 0.85mL/min; Elutriant A:H 2O/MeOH/HCO 2H100:5:0.05; Elutriant B:MeCN/HCOOH100:0.05; Gradient: 0min0%B; 0-1.2min100%B; 1.2min-1.50min100%B; UV detects: 210nm-500nm, resolving power 2nm.Before MS analyzed, this stream was split rear pillar (split postcolumn).
Following abbreviation has been used in whole this part: s=is unimodal; The bs=broad peak; The d=doublet; The dd=double doublet; The two triplets of dt=; The t=triplet; Tt=three triplets; The q=quartet; The m=multiplet; The Me=methyl; The Et=ethyl; The Pr=propyl group; The Bu=butyl; The M.p.=fusing point; The RT=retention time; MH +=molecular cation (that is the molecular weight of measurement).
Example I1:(N, N)-di-isopropyl 2-allyl benzene yl acetamide
Step 1:(N, N)-di-isopropyl 2-iodophenyl ethanamide
Figure BDA00003342326200321
Add successively in the adjacent iodobenzene acetic acid in methylene dichloride (85mL) (11.0g, 42.0mmol, the commercially available) solution oxalyl chloride (7.11mL, 84mmol) and 2 dimethyl formamides.At stirring at room solution 2h and in a vacuum solvent is removed.Absorb into this resistates in the methylene dichloride (100mL) and 0 ° of C cooling.(17.6mL 126mmol) and with this solution heats to room temperature to add Diisopropylamine then.In a vacuum solvent is removed.With the segmentation and use ethyl acetate extraction between ethyl acetate and water of this resistates.With the organic layer that merges with hydrogenchloride (1N), salt water washing, dry and concentrate with provide 14.3g (N, N)-di-isopropyl 2-iodophenyl ethanamide (white solid, 99%).C 14H 20INO, MW:345.23; LCMS (method A) RT1.90min; Quality 346 (100%, MH +), 268 (10%, MNa +); IR:2965,1634,1438,1369,1337cm -1; 1H NMR (400MHz, CDCl 3) δ 7.84 (d, 1H), 7.22-7.35 (m, 3H), 6.84-6.97 (m, 1H), 3.91 (m, 1H), 3.76 (s, 2H), 3.43 (m, 1H), 1.46 (d, 3H), 1.15 (d, 6H) ppm.
Step 2:(N, N)-di-isopropyl 2-allyl benzene yl acetamide
Figure BDA00003342326200331
To in toluene (17mL) (N, N)-di-isopropyl 2-iodophenyl ethanamide (step 1,0.235g, add in degassing 0.681mmol) (degassed) solution four (triphenylphosphines) close palladium (84mg, 0.072mmol).Gained solution is heated to 110 ° of C, continues 20h and cool down then.In a vacuum solvent is removed and with the segmentation and acetonitrile layer washed with hexane (2*30mL) between acetonitrile (30mL) and hexane (30mL) of the oil of yellow.Remove acetonitrile in a vacuum, and this resistates carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (9/1 to 4/1)), with provide (N, N)-di-isopropyl 2-allyl benzene yl acetamide (colourless oil, 250mg, 67%).C 17H 25NO; MW:259.39; LCMS (method A) RT1.97min; ES:260 (100%, MH +); IR.2965,1634,1466,1439,1369,1335cm -1; 1H NMR (400MHz, CDCl 3) δ 7.09-7.23 (4H, m), 5.95 (1H, m), 5.07 (1H, dd), 4.99 (1H, dd), 3.85 (1H, m), 3.66 (2H, s), 3.38-3.50 (1H, m), 3.36 (2H, d), 1.45 (7H, d), 1.08 (6H, d) ppm.
The replacement scheme of step 2:
To (the N in tetrahydrofuran (THF) (10mL), N)-di-isopropyl 2-iodophenyl ethanamide (step 1,0.50g, 1.44mmol) the degassing (degassed) solution in add four (triphenylphosphines) and close palladium (39mg, 0.034mmol), cesium fluoride (0.207mg, 1.40mmol) and tetramethyl ethylene ketone allyl group boric acid ester (0.229mg, 1.361mmol).Gained solution is heated to backflow 4h and adds water (20mL).Water layer is with extracted with diethyl ether and with the organic layer salt water washing that merges, dry and concentrated.This resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (9/1 to 4/1)), with provide (N, N)-di-isopropyl 2-allyl benzene yl acetamide (colourless oil, 135mg, 76%).Analytical data is identical with before coupling method.
Example I2:2-(2-allyl group-phenyl)-1-((2R, 5R)-2,5-dimethyl-tetramethyleneimine-1-yl)-ethyl ketone
Step 1: methyl 2-allyl acetic acid phenyl ester
Figure BDA00003342326200341
To the methyl 2-iodoacetic acid phenyl ester (1.00g in toluene (45mL), 3.62mmol, according to litt.Tetrahedron (" little tetrahedron ") 63,2007,9979 from corresponding acid preparation) add four (triphenylphosphines) the solution and close palladium (209mg, 0.0.181mmol) and allyl group tributyl first stannane (1.35mL, 4.34mmol).Gained solution is heated to 110 ° of C, continues 20h and cool down then.In a vacuum solvent is removed.With the segmentation and acetonitrile layer washed with hexane (2*30mL) between acetonitrile (30mL) and hexane (30mL) of the oil of yellow.Remove acetonitrile in a vacuum, and this resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (15/1)), to provide methyl 2-allyl acetic acid phenyl ester (colourless oil, 446mg, 65%).C 12H 14O 2; MW:190.24; LCMS (method A) RT1.74min; ES:191 (100%, MH +); IR.2951,1734cm -1; 1H NMR (400MHz, CDCl 3)
Figure BDA00003342326200342
-7.41 (4H, m), 5.99 (1H, m), 5.12 (1H, m), 5.03 (1H, m), 3.73 (3H, s), 3.72 (2H, s), 3.47 (2H, dt) ppm.
Step 2:2-allyl benzene guanidine-acetic acid
Figure BDA00003342326200343
To the methyl 2-allyl acetic acid phenyl ester in tetrahydrofuran (THF) (10mL) (step 1,0.400mg.2.10mmol) be added in the solution lithium hydroxide in the water (10mL) (0.097g, 2.31mmol).With this solution at stirring at room 3h and concentrate in a vacuum.Add water (40mL) and with pH regulator to 1.With this solution dichloromethane extraction and the organic layer that merges is dry and concentrated, to provide 2-allyl benzene guanidine-acetic acid (yellow oil, 363mg, 98%); C 11H 12O 2; MW:176.22; ES-175; IR1702cm -1; 1H NMR (400MHz, CDCl 3)
Figure BDA00003342326200351
-7.38 (4H, m), 5.99 (1H, m), 5.11 (1H, m), 5.04 (1H, m), 3.73 (2H, s), 3.47 (2H, dt) ppm.
Example I3:2-(2-allyl group-phenyl)-1-((2R, 5R)-2,5-dimethyl-tetramethyleneimine-1-yl)-ethyl ketone
Figure BDA00003342326200352
To the 2-allyl benzene guanidine-acetic acid (0.050mg in dimethyl formamide (5mL), 0.284mmol) solution in add 3-[3-(dimethylamino) propyl group successively]-1-ethyl-carbodiimide hydrochloride (EDCI, 0.075mmol, 0.397mmol), 1-hydroxyl-7-azepine benzotriazole (HOAt, 0.054mg, 0.397mmol), (2R, 5R)-dimethyl pyrrolidine (0.034mL, 0.298mmol), triethylamine (0.118mL, 0.851mmol).With this solution stirring 18h and interpolation water (20mL).Water layer is with extracted with diethyl ether and with the organic layer salt water washing that merges, dry and concentrated.This resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (9/1 to 4/1)), to provide 2-(2-allyl group-phenyl)-1-((2R, 5R)-2,5-dimethyl-tetramethyleneimine-1-yl)-ethyl ketone (colourless oil, 73mg, 99%).C 17H 23NO; MW:257.38; LCMS (method A) RT1.84min; ES258 (100%, MH +), 280 (10%, MNa +); 1H NMR (400MHz,
Figure BDA00003342326200353
-7.24 (4H, m), 5.97 (1H, m), 5.07 (1H, m), 4.99 (1H, m), 4.29 (1H, q), 4.01 (1H, q), 3.76 (1H, d), 3.58 (1H, d), 3.39 (2H, m), 2.08-2.26 (2H, m), 1.52-1.63 (2H, m), 1.23 (3H, d), 1.21 (3H, d) ppm.
Example I4:1,2a, 7,7a-tetrahydrochysene-2H-ring fourth [a] indenes-2-ketone
Method A(is via the formation of keteiminium)
Figure BDA00003342326200361
To (the N in methylene dichloride (10mL), N)-(example I1,0.100g 0.386mmol) add trimethylpyridine (0.061mL to di-isopropyl 2-allyl benzene yl acetamide successively in the solution, 0.463mmol), trifluoromethanesulfanhydride anhydride (0.072mL, 0.424mmol).With this solution at stirring at room 24h.In a vacuum solvent is removed and this resistates is absorbed in tetracol phenixin (4mL) and the water (4mL) and the mixture of this two phasic property is stirred 6h at 70 ° of C.With water layer dichloromethane extraction and the organic layer that merges is dry and concentrated.This resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (20/1)), to provide 1,2a, 7,7a-tetrahydrochysene-2H-ring fourth [a] indenes-2-ketone (colourless oil, 48mg, 74%); MW:158.22; LCMS (method A) RT1.51min; ES:159 (20%, MH +), 143 (100%); IR:29211777cm -1; 1H NMR (400MHz, CDCl 3) δ 7.29-7.36 (2H, m), 7.23-7.29 (2H, m), 4.65-4.80 (1H, m), 3.46 (1H, dd), 3.36 (1H), 3.11-3.19 (1H, and m) 3.08 (1H, d), 2.88 (1H, m) ppm.
* method B(is via the formation of ketene):
Figure BDA00003342326200362
To the 2-allyl benzene guanidine-acetic acid in methylene dichloride (25mL) (0.095g adds 1-chloro-N at 0 ° of C in solution 0.539mmol) for example I2, step 2, N, 2-trimethylammonium-1-allylamine (0.078mL, 0.593mmol).With this solution stirring 1h and be heated to backflow then.Then, under refluxing, slowly be added on triethylamine (0.082mL, 0.593mmol) solution in the methylene dichloride (4mL) in the solution of chloride of acid through two hours.With this reaction mixture restir 2h and cool down then.In a vacuum solvent is removed and this resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (20/1)), to provide 1,2a, 7,7a-tetrahydrochysene-2H-ring fourth [a] indenes-2-ketone (colourless oil, 56mg, 66%).Analytical data is identical with the product that usefulness method A obtains.
Example I5: tetrahydrochysene indeno [1,2-b] furans-2-ketone derivatives:
Example 1: racemize-tetrahydrochysene indeno [1,2-b] furans-2-ketone
Figure BDA00003342326200371
Will be in acetic acid (5mL) and water (0.5mL) 1,2a, 7,7a-tetrahydrochysene-2H-ring fourth [a] indenes-2-ketone (example I4,0.377mg, 2.383mmol) solution 0 ° of C cooling and add hydrogen peroxide (in water 30%, 0.810mL, 7.14mmol).This solution is poured in the saturated solution of sodium bicarbonate at 0 ° of C stirring 3h and with this reaction mixture.This solution is with ethyl acetate extraction and with the organic layer salt water washing that merges, dry and concentrated.This resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (4/1)), to provide racemize-tetrahydrochysene indeno [1,2-b] furans-2-ketone (colourless oil, 383mg, 92%), its cooling solidifies namely that (data and litt data are complementary, CAS4471-33-4).C 11H 10O 2; MW:174.20; LCMS (method A) RT1.32min; ES:175 (60%, MH +), 129 (100%); IR:1769cm -1; 1H NMR (400MHz, CDCl 3) δ 7.50 (1H, d), 7.25-7.39 (4H, m), 5.91 (1H, d), 3.28-3.45 (2H, m), 2.86-2.97 (2H, m), 2.41 (1H, dd) ppm.
Example 2:3a (R), 8b (S) tetrahydrochysene indeno [1,2-b] furans-2-ketone:
Figure BDA00003342326200372
This asymmetric lactone is to use aforesaid method A(example I4 for cyclobutanone formation and Bayer-Villiger (Baeyer Villiger) oxidation) from 2-(2-allyl group-phenyl)-1-((2R, 5R)-2,5-dimethyl-tetramethyleneimine-1-yl)-ethyl ketone (example I3) acquisition.Analyze to determine that this enantiomer is excessive by following chirality HPLC: be fixed on the 5 μ m silica gel
Figure BDA00003342326200381
IC post (cellulose iii (3,5-dichlorophenyl carbamate), 0.46cm x25cm, DAD wavelength (nm): 270); Solvent gradient: heptane/2-propyl alcohol/0.1%DEA97/03/0.1; Flow velocity 1mL/min; Retention time enantiomer 1:32min(96%), enantiomer 2:38min(4%); Ee=92%; [ ] D=-107 ° of (litt:J.Agric.Food Chem.(" agriculturals and food chemistry periodical ") 1997,2278-2283).
Example I6:(1-oxo-dihydro indenes-2-yl)-the methyl acetate derivative
Example I6 (a): (1-oxo-dihydro indenes-2-yl)-methyl acetate (H1)
Step 1:(1-oxo-dihydro indenes-2-yl)-acetic acid
Figure BDA00003342326200382
((0.051g 1.26mmol) also is heated to 100 ° of C with this solution to tetrahydrochysene indeno [1,2-b] furans-2-ketone among the Xiang Zaishui (20mL), keeps one hour to add sodium hydroxide in suspension 1.15mmol) for example I5 or commercially available, 0.200g.The cooling of this solution is down to room temperature and add ruthenium chloride (III) hydrate (0.048g, 0.230mmol), dropwise be added on subsequently sodium periodate in the water (5mL) (0.368mg, 1.72mmol).With this solution at stirring at room 1h and add Virahol (0.2mL).Use 2M HCl that pH is acidified to 1 and this reaction filtered.Filtrate is with methylene dichloride (3*30mL) extraction and with organic layer water (30mL) washing that merges, dry and concentrate, to provide (1-oxo-dihydro indenes-2-yl)-acetic acid (light yellow solid, 170mg, 78%).C 11H 10O 3; MW:190.2.LCMS (method A) RT1.16min; ES-189 (35%, MH +), 175 (70%), 145 (100%), 127 (90%). 1H?NMR(400MHz,
Figure BDA00003342326200383
(1H,d),7.65(1H,t),7.54(1H,d),7.41(1H,t),3.39-3.51(1H,m),2.83-3.02(3H,m),2.70(1H,m)ppm。
Step 2:(1-oxo-dihydro indenes-2-yl)-methyl acetate (H1)
Figure BDA00003342326200391
(step 1 2.00g) is added sulfuric acid (2mL) at 0 ° of C in the solution to (1-oxo-dihydro indenes-2-yl)-acetic acid in methyl alcohol (10mL).With this solution stirring 2h and then water (50mL) dilute and use ethyl acetate extraction.The organic layer of these merging is washed with saturated sodium bicarbonate, dry and concentrate, with provide (1-oxo-dihydro indenes-2-yl)-methyl acetate (light yellow oil, 2.15g, quantitatively).C 12H 12O 3; MW:204.23; LCMS (method A) RT1.40min; ES227 (25%, MNa +), 205 (25%, MH +), 173 (100%); IR:2952,1734,1710,1608,1436cm -1; 1H NMR (400MHz, CDCl 3) 7.78 (1H, d), 7.61 (1H, t), 7.47 (1H, d), 7.39 (1H, t), 3.70 (3H, s), 3.47 (1H, dd), 2.95-3.08 (2H, m), 2.89 (1H, dd), 2.63 (1H, dt) ppm.This compound is used for next step and need not be further purified.
Example I6 (b): methyl 2-(5-fluoro-1-oxo-dihydro indenes-2-yl) acetic ester (H2)
Compound in this example is by a kind of Journal of being described in of Agricultural and Food Chemistry(" agricultural and food chemistry magazine ") (1997), 45 (6), 2278-2283 and Journal of Agricultural and Food Chemistry(" agricultural and food chemistry magazine ") (1992), 40 (7), the currently known methods among the 1230-5 synthesizes.
Step 1:5-fluoro-1-oxo-dihydro indenes-2-carboxylicesters
Figure BDA00003342326200392
With sodium hydride (800mg, 19.9mmol is in mineral oil 60%) with HPLC level hexane wash (twice).(1.57g, 1.6ml is 13.3mmol) and with the solution that generates one hour (this reaction mixture turns green) of refluxing to add dried benzene (4.2ml) and diethyl carbonate.In this reflux solution through 45min slowly be added on 5-fluoro-dihydro indenes-1 ketone in the benzene (2.7ml) (1.0g, 6.66mmol).The reaction mixture that generates was refluxed one hour again.After this reaction is finished, add acetic acid/water (50/50, about 20ml) up to all solids dissolving (pH-5).Water layer is extracted three times with benzene.With organic moiety water, the saturated brine washing that merges, with dried over sodium sulfate and evaporate to dryness.This crude product is carried out purifying by column chromatography (using ethyl acetate/hexane (5%)), to obtain desirable product (1.3g, 94%).
Step 2:2-(2-oxyethyl group-2-oxo-ethyl)-5-fluoro-1-oxo-dihydro indenes-2-Eufin
Figure BDA00003342326200401
(1.4g, 6.3mmol), sodium hydride (278mg, 6.9mmol is in mineral oil 60%) and DMF(do, ° C of mixture heating up to 65 2.5ml) kept one hour with 5-fluoro-1-oxo-dihydro indenes-2-Eufin.Be added in identical temperature and do DMF(4.0ml) in bromo ethyl ester (1.15g, 0.8ml, 6.9mmol) solution and continue heating 3h again.After finishing this reaction, with the reactive material evaporate to dryness, add 5ml water and with this suspension with ethyl acetate extraction (25ml x3).With the organic layer salt water washing that merges, use dried over sodium sulfate, evaporation and use ethyl acetate/hexane (15%) are carried out column chromatography, to obtain desirable product (1.3g, 72%).
Step 3:(5-fluoro-1-oxo-dihydro indenes-2-yl)-acetic acid
Figure BDA00003342326200402
(500mg 1.6mmol) is suspended in the 6N HCl of 1.4ml: in acetic acid (1:1) mixture and be heated to backflow 3h with 2-(2-oxyethyl group-2-oxo-ethyl)-5-fluoro-1-oxo-dihydro indenes-2-Eufin.By the TLC monitoring reaction.With the reactive material evaporate to dryness, add 10ml water and extract with ethyl acetate (40ml x3).Organic layer is washed with saturated brine, use dried over sodium sulfate.With the crude product hexane wash, to obtain desirable product (280mg, 82%).
Step 4:2-(5-fluoro-1-oxo-dihydro indenes-2-yl) methyl acetic acid ester H2
Figure BDA00003342326200411
(280mg 1.3mmol) absorbs in the 10ml methyl alcohol (HPLC level), is cooled to 0 ° of C and dropwise is added into the vitriol oil of 0.5ml in this solution and is heated to backflow 5h with (5-fluoro-1-oxo-dihydro indenes-2-yl)-acetic acid.By the TLC monitoring reaction.After this reaction is finished, with reactive material evaporation, add 10ml water and extract with ethyl acetate (25ml x3).Ethyl acetate is partly used saturated water-based sodium bicarbonate, salt water washing, drying (sodium sulfate) and under reduced pressure concentrated.This crude product is carried out purifying by column chromatography (using acetone/hexane (8%)), to obtain desirable product H2(230mg, 77%).
Use this method to prepare compound H 2 to H8(table H).
Example I6 (c): (1-oxo-4-bromo-dihydro indenes-2-yl)-methyl acetate H9
Figure BDA00003342326200412
At-78 ° of C, (15.8g 75mmol) adds LiHMDS(1M in THF, 90mL) in the solution to 4-bromine indone.Permission should be heated to 0 ° of C by amber solution, and is cooled to-75 ° of C again, and dropwise add the 2-ethyl bromoacetate (9.1mL, 82mmol).Allow this mixture to heat to spend the night (75 ° of C are to-20 ° of C, through 12h).This mixture is carried out cancellation with saturated ammonium chloride, and use ethyl acetate extraction.Flash chromatography provide 19.5g, with initial indone 2-[4-bromo-2-(2-oxyethyl group-2-oxo-ethyl)-1-oxo-dihydro indenes-2-yl] title compound in the mixture of ethyl acetate H9, and use it in the next step and need not be further purified (pure, 60% desirable product).
Use this method to prepare compound H 9 and H10(table H).
Example I7:3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone
Example I7 (a): 3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone G1
Figure BDA00003342326200421
Method A
In anhydrous methanol with ammonium acetate (3.77g, 48.9mmol) solution coevaporation.Then, be added on (1-oxo-dihydro indenes-2-yl)-methyl acetate H1(1.00g in the methyl alcohol (40mL) successively, 4.89mmol), molecular sieve (4.9g).With this solution stirring 30min and add sodium cyanoborohydride (0.92g, 14.9mmol).With this suspension returning 40h.This solution is passed through diatomite filtration.Add saturated solution of sodium bicarbonate and use ethyl acetate (3*50mL) to extract this solution.With organic layer hydrogenchloride (1N), the salt water washing of these merging, dry and concentrated.This resistates is carried out purifying by flash chromatography (with ethyl acetate and be that ethyl acetate/methanol (95/5) is carried out wash-out then), to provide 3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone G1(white solid, 300mg, 35%).LCMS (method A) RT1.17; ES196,174; IR3233,1689cm -1; Mp:150-153 ° of C; 1H NMR (400MHz, CD 3OD)
Figure BDA00003342326200422
(1H, d), 7.12-7.27 (3H, m), 5.04 (1H, d), 3.22-3.37 (2H, m), 2.83 (1H, d), 2.70 (1H, dd), 2.15 (1H, dd) ppm.
Method B
Figure BDA00003342326200431
To the 1-oxo in methyl alcohol (100mL)-dihydro indenes-2-base-methyl acetate H1(8.55g, add in solution 41.89mmol) sodium acetate (5.15g, 62.8mmol) and oxammonium hydrochloride (4.36g, 62.8mmol).This solution is heated to 65 ° of C, keeps 12h, dilute with water is used ethyl acetate extraction, uses the salt water washing, and is dry and concentrated, to provide corresponding oxime (8.00g, 87%).Absorb into this resistates in the acetic acid (70mL) and be heated to 60 ° of C.Then, (protionwise) adds zinc powder (23.8g 364mmol), maintains the temperature under 80 ° of C in batches.This solution is stirred 30min and filtration then at 60 ° of C.Be added into water in this filtrate and this solution neutralized with solid carbonic acid potassium and reach 7 up to pH.With this solution dichloromethane extraction, use HCl(1N) washing, dry and concentrated, to be given the lactan G1(3.9g of white solid, 61%).Data are identical with method A.
Use this method to prepare compound G1 to G10(and show G).
Example I7 (b): 7-nitro-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone
Figure BDA00003342326200432
(72mL) is added into nitric acid (63.5mmol with sulfuric acid, 4.4mL) and the mixture of the cooling of water (11.3mL) in, and with this mixture dropwise be added in Nitromethane 99Min. (100mL) 3,3a, 4, (10g is in cold (2 ° of C-8 ° of C) suspension 57.7mmol) for 8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone.After adding end, this mixture is stirred 1.5h at 2 ° of C-8 ° of C, and it is poured on the mixture of ice and water (1L).This white suspension was stirred one hour, filter and wash with water.This white solid is suspended in the 1L ethyl acetate, dry and concentrated under vacuum.Obtain 7-nitro-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone (9.2g, 73%).1H?NMR(400MHz,CD 3OD)
Figure BDA00003342326200441
-8.08(2H,m),7.39(1H,d),6.89(1H,brs),5.09(1H,d),3.49-3.37(2H,m),2.93(1H,d),2.78(1H,dd),2.26(1H,dd)ppm。
Example I8:2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrrole derivative:
Example I8 (a): 2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F1
Figure BDA00003342326200442
To in anhydrous acetonitrile (10mL) 3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone G1(0.100g, add in suspension 0.578mmol) dimethyl aminopyridine (0.007mg, 0.057mmol), triethylamine (0.161mL, 1.15mmol) and tert-Butyl dicarbonate (245mmol, 1.15mmol in the 1mL methylene dichloride).With this solution at stirring at room 6h.With this solution with ethyl acetate dilution and with hydrogenchloride (1M) and salt water washing.The organic layer of these merging is dry and concentrated.This resistates is carried out purifying by flash chromatography (carrying out wash-out with ethyl acetate and hexanaphthene (7/3)), to provide viscous oil F1(160mg, quantitatively).C 16H 19NO 3; MW:273.33; LCMS (method B) RT1.74min; ES:296 (MNa +), 174 (MH +-Boc), 129; IR:2978,1782,1747,1709cm -1; 1H NMR (400MHz, CDCl 3)
Figure BDA00003342326200443
(1H, d), 7.19-7.34 (3H, m), 5.62 (1H, d), 3.08-3.26 (2H, m), 2.84 (1H, d), 2.78 (1H, dd), 2.29 (1H, dd), 1.63 (9H, s) ppm.
Use this method to prepare compound F 17-hydroxy-corticosterone 1 to 10(table F).
Example I8 (b): 5-cyano group-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F11
To at DMF(30mL) in 5-bromo-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F9(1.5g 4.25mmol) adds Pd (PPh3) in the solution 4(751mg, 0.63mmol) and Zn (CN) 2(1.00g, 8.51mmol).This solution is stirred 16h at 100 ° of C.After the cooling, add water and with this solution ethyl acetate extraction.Organic layer is with salt water washing three times, dry and concentrated.This roughage is dissolved in the 50ml acetonitrile, in this acetonitrile, is added with Boc 2O(5.5g, 25.2mmol), NEt 3(6ml) and DMAP(520mg, 4.26mmol).The mixture of this generation is stirred 16h.This dark-brown solution is concentrated under vacuum, and this resistates is dissolved in the ethyl acetate.With organic layer HCl(1N), the salt solution washed twice, dry and under vacuum, concentrate.This resistates is carried out purifying by flash chromatography (carrying out wash-out with ethyl acetate and hexanaphthene (10/90 to 30/70 through 30min.)), be the desirable compound F 17-hydroxy-corticosterone 11(69% of cream-coloured colloid with what provide 880mg).LCMS(method E): 0.87min; ES+:619[2M+Na].
Use this method to prepare F12 and prepare the compound (table F) of F11 from F9 from F10.
Example I8 (c): 8-allyl group-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F14
Figure BDA00003342326200452
With the 8-bromo-2-oxo-3 in toluene (17mL), 3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester (example F10,700mg), Pd (PPh 3) 4The solution of (280mg, 0.12 equivalent), allyl tributyltin acid esters (1.65g, 2.5 equivalents) outgases and stirs under refluxing and spend the night.Under vacuum with removal of solvents.Absorb into this resistates in the acetonitrile (40mL) and use the normal hexane washed twice.Remove acetonitrile in a vacuum, and this resistates is carried out purifying by flash chromatography (carrying out wash-out with ethyl acetate and hexanaphthene (1% to 25%)), with desirable product (allyl group and mixture of isomers) the F14:LCMS(method E that provides 350mg), RT:1.06min, [ES+[377, M+CH 3CN+Na].
Use this method to prepare F13 and prepare the compound (table F) of F14 from F10 from F9.
Example I8 (d): 8-propyl group-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F15
Figure BDA00003342326200461
With the 2-oxo-3 of packing in the flask of crossing with argon cleaning, 3a, 4,8b-tetrahydrochysene-2H-4-allyl group-indeno [1,2-b] and pyrroles-1-carboxylic acid tert-butyl ester F14 and isomer (200mg, 0.63mmol), ethyl acetate (4mL) and Pd/C(10%, 30mg).At H 2Under the atmosphere, with this black suspension at stirring at room 72h.Then this suspension is filtered at the diatomite liner, and filtrate is concentrated under vacuum, be used in 1% in the hexanaphthene to 10% gradient ethyl acetate and carry out purifying by flash chromatography, to be given a kind of desirable compound F 17-hydroxy-corticosterone 15(120mg of water white oil, 60%).LCMS(method E): 1.14min; ES+:338 (M+Na +).
Example I8 (e): 1-(4-chloro-phenyl-)-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-2-ketone F16
Figure BDA00003342326200471
Tetrahydrochysene among the Xiang Zaishui (3mL)-1H-indeno [1,2-b] pyrroles-2-ketone (1.00g, 5.77mmol) solution in add Red copper oxide (I) (167mg), to chloroiodobenzone (1.38g, 5.77mmol), Tetrabutyl amonium bromide (0.372g, 1.15mmol) and potassiumphosphate (2.45g, 11.5mmol).This suspension is spent the night 130 ° of C vigorous stirring.This mixture is cooled down and dilute with methylene dichloride.Solid filtering fallen and organic layer is dry and concentrate.This resistates is used in 1% in the hexanaphthene to 60% gradient ethyl acetate passes through purified by flash chromatography, to be given desirable product F16(600mg, 39%).LCMS(method A) 1.72min; ES+:284 (M+H +).
Use this method to prepare compound F 17-hydroxy-corticosterone 16-F19.
Example I8 (f): 6-(2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-yl) pyridine-3-nitrile F20
Figure BDA00003342326200472
At 0 ° of C, in toluene (15ml) 3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone (1g, add in suspension 5.77mmol) sodium hydride (0.254g, 6.35mmol).With this batch heat to room temperature and add 2-chloro-5-cyanopyridine (0.824g, 5.77mmol).Should criticize at 95 ° of C and stir 2h.After the cooling, extract to this batch interpolation frozen water and with ethyl acetate (2x).The organic phase that merges is concentrated and resistates is carried out purifying by column chromatography (hexane/ethyl acetate 7/3), to provide 6-(2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-yl) pyridine-3-nitrile F20(1.00g, 63%).LCMS(method A) 1.68min; ES+:276 (M+H +).
Example I8 (g): ((3aR, 8bS)-1-thiazol-2-yl-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-2-ketone
F21
Figure BDA00003342326200481
In the Zai diox (6mL) (3aR, 8bS)-3,3a, 4, (0.500g adds potassiumphosphate (1.26g to 8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone in solution 2.89mmol), 5.77mmol), cuprous iodide (0.055g, 0.289mmol), the 2-bromo thiazole (0.473g, 2.89mmol) and N, N'-dimethyl ethane-1, the 2-diamines (0.0254g, 0.288mmol).This yellow solution is heated to backflow to spend the night.Then this suspension is diluted and filtration with ethyl acetate.In a vacuum solvent is removed and this resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (0-50%)), to be given a kind of title compound ((3aR of water white oil, 8bS)-1-thiazol-2-yl-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-2-ketone F21(0.390g, 1.52mmol, 52.7% yield).LCMS(method A) 1.66min; ES+:257 (M+H +).
Example I8 (h): 3aR, 8bS)-1-allyl group-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-2-ketone F22
At 0 ° of C, at DMF(10ml) in (3aR, 8bS)-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone (1.00g, add in solution 5.77mmol) sodium hydride (in mineral oil 60%, 0.254g, 6.35mmol).At 0 ° of C, with this solution stirring 1h and add allyl bromide 98 (1.41g, 2 equivalents, 1.01mL, 11.5mmol).With this solution at stirring at room 18h and add water.With this mixture ethyl acetate extraction and water and salt water washing.In a vacuum solvent is removed and this resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (50:50)), to be given a kind of (3aR of water white oil, 8bS)-1-allyl group-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-2-ketone F22(0.910g, 0.910g, 4.27mmol, 73.9% yield).LCMS(method A) 1.51min; ES+:214 (M+H +).
According to this method use 4-fluorobenzyl chloride, 2-bromoacetonitrile, Vinyl chloroformate as alkanisation reagent preparation compound F 17-hydroxy-corticosterone 23 to F25.
Example I8 (i): (3aR, 8bS)-2,4-dioxy-3a, 8b-dihydro-3H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F26
To the 2-oxo-3 in acetone (90mL) and water (20mL), 3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F1(5.00g adds KMnO4(14.7g in solution 18.2mmol), 93mmol).With this solution in stirring at room 48h and filtration.With this solution concentration to half volume and add hypo solution (2%, 50mL).With this solution ethyl acetate extraction, use the salt water washing, dry and concentrated.This resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (7/3)), to provide desirable product F26(1.6g, 30%).LCMS(method E): 0.81min; ES+:597 (2M+Na +).
Example I8 (j): (3aR, 4R, 8bS)-and 4-hydroxyl-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F27
Figure BDA00003342326200501
At 0 ° of C, at ethanol (20mL) and THF(20mL) (3aR, 8bS)-2,4-dioxy-3a, 8b-dihydro-3H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F26(1.60g adds NaBH in solution 5.56mmol) 4(0.316g, 8.15mmol).This solution is stirred 2h at 0 ° of C.The careful 1MHCl and this solution is concentrated in a vacuum that adds.With the segmentation and use ethyl acetate extraction between ethyl acetate and water of this resistates.With the salt water washing of the organic layer of these merging, dry and concentrated.This resistates is carried out purifying by flash chromatography (2/1 cyclohexane/ethyl acetate), to provide (3aR, 4R, 8bS)-4-hydroxyl-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F27(800mg, 50%).LCMS(method E): 0.78min; ES+:601 (2M+Na +).
Example I8 (k): (3aR, 4S, 8bS)-and 4-fluoro-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F28
Figure BDA00003342326200502
At 0 ° of C, to at methylene dichloride (1 equivalent, 3mL, the 0.69mmol) (3aR in, 4R, 8bS)-and 4-hydroxyl-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester (0.200g, add in solution 0.691mmol) diethylaminosulfur trifluoride (0.913mL, 6.91mmol).This solution is stirred 30min at 0 ° of C.This reaction mixture is used saturated NaHCO carefully 3Cancellation and use dichloromethane extraction.Organic layer is dry and concentrated.This resistates is carried out purifying by flash chromatography (the 0-80% ethyl acetate in hexanaphthene), to provide desirable product F28(0.150g, 74%).LCMS(method A): 1.65min; ES+:605 (2M+Na +).
Example I8 (l): 4-acetoxyl-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F29
Figure BDA00003342326200511
To the 2-oxo-3 in methylene dichloride (9mL), 3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester (1.28g, add in solution 4.68mmol) para toluene sulfonamide (0.164g, 0.937mmol), iodobenzene diacetate (3.85g, 11.7mmol) and iodine (0.238g, 0.937mmol).With this solution under argon gas, at 60 ° of C heating 2h.Room temperature is down in this solution cooling, and adds saturated sodium sulfite (2mL).Add water and use methylene dichloride (3*50mL) to extract this solution, drying also concentrates.This resistates is carried out purifying by flash chromatography (10% to 90% ethyl acetate in hexanaphthene), to be given a kind of non-enantiomer mixture (2:1, be conducive to trans) 4-acetoxyl-2-oxo-3,3a, 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F29(0.900g, 58.%).These isomer can not be separated.LCMS(method E): 0.90min; ES+:685 (2M+Na +).
Example I9:3-[1-dimethylamino-first-(Z)-subunit]-2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester E1's is synthetic
Figure BDA00003342326200521
With the 2-oxo-3 in two (dimethylamino) methane of tert.-butoxy, 3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester F1(160mg, 0.586mmol) solution is at 75 ° of C heating 4h.This solution is with ethyl acetate dilution and water, salt water washing, dry and concentrate, to provide 3-[1-dimethylamino-first-(Z)-subunit]-2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester E1(colorless solid, 190mg, 98%).C 19H 24N 2O 3; MW:328.41; LCMS (method A) RT1.78min; ES:329 (MH +), 273; 1H NMR (400MHz, CDCl 3)
Figure BDA00003342326200522
(1H, d), 7.15-7.26 (4H, m), 5.61 (1H, d), 3.99 (1H, td), 3.37 (1H, dd), 3.10 (6H, s), 3.06 (1H, dd), 1.60 (9H, s) ppm.
Use this method to prepare compd E 1 to E15(table E)
Example I10:3-[1-hydroxyl-first-(Z)-subunit]-2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrrole derivative synthetic:
Example I10 (a): 3-[1-hydroxyl-first-(Z)-subunit]-2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester D1
Figure BDA00003342326200523
To the 3-[1-dimethylamino-first in tetrahydrofuran (THF) (2mL)-(Z)-subunit]-2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester E1(190mg, add in solution 0.579mmol) hydrogenchloride (1M, 0.87mL).With this solution at stirring at room 3h.This solution is with ethyl acetate dilution and water, salt water washing, dry and concentrate.This resistates is ground with ethyl acetate, to provide 3-[1-hydroxyl-first-(Z)-subunit]-2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester D1(white powder, 140mg, 80%).C 17H 19NO 4; MW:301.35; LCMS (method A) RT1.72min; ES:302 (MH +), 246; 1H NMR (400MHz, DMSO-d6) (1H, s), 7.54 (1H, d), 7.42 (1H, d), 7.13-7.31 (3H, m), 5.59 (1H, d), 3.70 (1H, m), 3.22 (1H, dd), 3.15 (1H, dd), 1.53 (10H, s) ppm.
Use this method to prepare Compound D 1 to D10 and D25(table D).
Example I10 (b): (3Z)-5-propyl group-3-(dimethyl-amino-methylene)-2-oxo-4,8b-dihydro-3aH-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester D11's is synthetic
Figure BDA00003342326200532
(3Z)-5-allyl group-3-(the dimethyl-amino-methylene)-2-oxo-4 of packing in the flask of crossing with argon cleaning, 8b-dihydro-3aH-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester D10(98mg, 0.29mmol) and Pd/C(10%, 40mg) and ethyl acetate (6mL).At H 2Under the atmosphere, with this black suspension at stirring at room 24h.This suspension is filtered at the diatomite liner, and yellow filtrate is concentrated under vacuum, to be given the title compound D11(47mg of brown colloid, 47%).LCMS (method E): RT:1.06min; ES-342[M-H]
Example I10 (c): (3E)-3-(hydroxyl methylene radical)-2-oxo-4,8b-dihydro-3aH-indeno [1,2-b] pyrroles-1-carboxylic acid, ethyl ester D12's is synthetic
With 2-oxo-3,3a, (200mg 0.81mmol) is dissolved in the tetrahydrofuran (THF) (8mL) 4,8b-tetrahydrochysene indeno [1,2-b] pyrroles-1-carboxylic acid, ethyl ester, is cooled to-78 ° of C.Then, and two (TMS) amidation lithiums of interpolation (1mol/L in THF, 1.22mL, 1.22mmol).Behind-78 ° of C1h, and the interpolation ethyl formate (0.198mL, 2.446mmol).With this mixture restir 30min and allow then it is heated to room temperature.Behind 30min again, add water.With this mixture extracted with diethyl ether, with the pH regulator to 1 of water layer, and with this solution EtOAc(2*20mL) extraction, dry (Na 2SO 4) and concentrate, with (3E)-3-(hydroxyl the methylene radical)-2-oxo-4 that is given water white oil, 8b-dihydro-3aH-indeno [1,2-b] pyrroles-1-carboxylic acid, ethyl ester D12(120mg, 54%), use it for next step and further purifying.LCMS (method A): RT:1.53min; ES-272[M-H]
Prepare following Compound D 12-D21, D23 and D24 according to this method.
Example D22:(3E)-and 1-ethanoyl-3-(hydroxyl methylene radical)-4,8b-dihydro-3aH-indeno [1,2-b] pyrroles-2-ketone D22's is synthetic
To at methylene dichloride (5mL, 0.497mmol) in (3E)-3-(hydroxyl methylene radical)-1,3a, 4,8b-tetrahydrochysene indeno [1,2-b] (100mg 0.497mmol) adds N to pyrroles-2-ketone in the solution, N-lutidine-2-amine (6mg, 0.05mmol), N, N-diethyl ethamine (0.20mL, 1.49mmol), diacetyl oxide (0.152g, 1.49mmol).With this solution at stirring at room 24h.This mixture is washed with the methylene dichloride dilution and with 1N HCl.This organic layer is dry and concentrate and this resistates is carried out purifying by flash chromatography (0-100%EtOAc in CyH), with provide [(E)-(1-ethanoyl-2-oxo-4,8b-dihydro-3aH-indeno [1,2-b] pyrroles-3-subunit) methyl] acetic ester (45mg, 31%) (LCMS (method A): RT:1.69min; ES+286 (M+H +)).To the preceding material in methyl alcohol (1mL) (40mg, add in solution 0.14mmol) salt of wormwood (0.019g, 0.14mmol).This solution stirring 30min and interpolation 1N HCl(2 are dripped).Add water (20mL) and with this solution EtOAc(2*20mL) extraction, dry and concentrate, to provide a kind of white solid (35mg, quantitative), use it for next step and further purifying.LCMS (method A): RT:1.53min; ES-272[M-H].
Example I11:3-[1-hydroxyl-first-(Z)-subunit]-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone (C1) synthetic
Method A:
At 0 ° of C, to the 3-[1-hydroxyl-first in methylene dichloride (20mL)-(Z)-subunit]-2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester D1(0.400g adds trifluoroacetic acid (2mL) in solution 1.32mmol).With this solution stirring 1h.Add saturated sodium hydrogen carbonate solution and with the water layer dichloromethane extraction.The organic layer of these merging is with saturated sodium hydrogen carbonate solution washing, dry and concentrate in a vacuum, to provide 3-[1-hydroxyl-first-(Z)-subunit]-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone C1(white solid, 271mg, quantitatively).C 12H 11NO 2; MW:201.23; LCMS (method A) RT1.18min; ES:256 (MH ++ MeCN), 224 (MNa +), 202 (MH +); IR:3264,1678cm -1; 1H NMR (400MHz, DMSO-d6) (1H, s), 7.16-7.38 (4H, m), 7.13 (1H, d), 4.94 (1H, d), 3.68-3.82 (1H, m), 3.31 (2H, dd), 3.01 (1H, dd) ppm.
Use this method to prepare Compound C 1 to 10(table C)
Method B:
Figure BDA00003342326200561
3-[1-dimethylamino-first in the Zai diox (50mL)-(Z)-subunit]-2-oxo-3,3a, 4,8b-tetrahydrochysene-2H-indeno [1,2-b] pyrroles-1-carboxylic acid tert-butyl ester D1(1.68g adds HCl(37% in solution 4.63mmol), 8.37mL).This solution at stirred overnight at room temperature and dilute with water then, is used ethyl acetate extraction, use the salt water washing, dry and concentrate, to provide the 3-[1-hydroxyl-first identical with method A-(Z)-subunit]-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone C1(0.85g, 78%).
Use this method preparation: C1, C11 to C14(show C).
Example P1 and P2 (3aR*, 8bS*, 5 ' R*)-3-[1-(4-methyl-5-oxo-2,5-dihydro-furan-2-base oxygen base)-first-(E)-subunit]-3,3a, 4, diastereomer and (3aR*, the 8bS* of 8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone (P1), 5 ' S*)-3-[1-(4-methyl-5-oxo-2,5-dihydro-furan-2-base oxygen base)-first-(E)-subunit]-3,3a, 4, synthesizing of the diastereomer of 8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone (P2).
Figure BDA00003342326200562
To at the 3-[1-hydroxyl-first in dimethyl formamide (5mL) of 0 ° of C cooling-(Z)-subunit]-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone C1(0.130g, add in solution 0.646mmol) potassium tert.-butoxide (0.086g, 0.711mmol).With this solution stirring 10min, and be added on bromo butenolide in the tetrahydrofuran (THF) (1mL) (0.137mg, 0.775mmol is according to Johnson(Jansen) ﹠amp; Everyone, J.C.S.Perkin(pul gold) I, 1981,1734-1743) preparation) solution.This solution is stirred 3h at 0 ° of C.With the segmentation and with this water layer ethyl acetate extraction between ethyl acetate and water of this solution.With the salt water washing and concentrated of the organic layer of this merging.This resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (1/4)).Obtained two kinds of diastereomers:
-(3aR*, 8bS*, 5 ' R*)-3-[1-(4-methyl-5-oxo-2,5-dihydro-furan-2-base oxygen base)-first-(E)-subunit]-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone P1(polarity is lower, 50mg, 26%); C 17H 15NO 4; MW:297.31; Mp200 ° of C; LCMS (method A) RT1.52min; ES:339 (MH ++ MeCN), 298 (MH +); 1H NMR (400MHz, CDCl 3) δ 7.18-7.34 (5H, m), 6.96 (1H, s), 6.94 (1H, br.s.), 6.16 (1H, s), 5.12 (1H, d), 3.91 (1H, tt), 3.46 (1H, dd), 3.09 (1H, dd), 2.02 (3H, s) diastereomers of ppm.
-(3aR*, 8bS*, 5 ' S*)-3-[1-(4-methyl-5-oxo-2,5-dihydro-furan-2-base oxygen base)-first-(E)-subunit]-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone P2(polarity is higher, 50mg, 26%); C 17H 15NO 4; MW:297.31; Mp213 ° of C; LCMS (method A) RT1.51min; ES:339 (MH ++ MeCN), 298 (MH +); 1H NMR (400MHz, CDCl 3) δ 7.11-7.38 (5H, m), 6.96 (1H, s), 6.73 (1H, br.s.), 6.15 (1H, s), 5.12 (1H, d), 3.91 (1H, tt), 3.44 (1H, dd), 3.08 (1H, dd), 2.02 (3H, s) diastereomers of ppm.
Prepare compd A 2 to A27 and B2 to B27 according to identical method.A2-A27 is the lower diastereomer of polarity (referring to Table A); B2-27 is the higher diastereomer of polarity (referring to table B).
Example A27:(3E)-and the 1-[(4-fluorophenyl) methyl]-3-[(4-methyl-5-oxo-2H-furans-2-yl) formaldehyde]-4,8b-dihydro-3aH-indeno [1,2-b] pyrroles-2-ketone A27 and (3E)-1-[(4-fluorophenyl) methyl]-3-[(4-methyl-5-oxo-2H-furans-2-yl) formaldehyde]-4,8b-dihydro-3aH-indeno [1,2-b] pyrroles-2-ketone B27's is synthetic
Figure BDA00003342326200581
To (the 3E)-1-[(4-fluorophenyl in methylene dichloride (10mL)) methyl]-3-(hydroxyl methylene radical)-4,8b-dihydro-3aH-indeno [1,2-b] pyrroles-2-ketone (60mg, 0.1940mmol) solution in add 2-bromo-4-methyl-2H-furans-5-ketone (51mg, 0.291mmol) and Hunig alkali (0.064mL, 0.39mmol).With this solution in stirred overnight at room temperature and in a vacuum solvent is removed.This resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene and ethyl acetate (1:4)), to provide the fluorophenyl as (3E)-1-[(4-) methyl]-3-[(4-methyl-5-oxo-2H-furans-2-yl) formaldehyde]-4,8b-dihydro-3aH-indeno [1,2-b] pyrroles-2-ketone A27 and B27(30mg, 38%) the desirable product of mixture of diastereomer.LCMS(method A) RT1.85min; ES:406 (M+H +).
Prepare compd A 28, B28, A29 and B29(Table A and B according to this method).
Example P3:1-methyl-(3aR*, 8bS*, 5 ' R*)-3-[1-(4-methyl-5-oxo-2,5-dihydro-furan-2-base oxygen base)-first-(E)-subunit]-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone synthetic
Figure BDA00003342326200582
To (the 3aR* in dimethyl formamide (1mL), 8bS*, 5 ' R*)-3-[1-(4-methyl-5-oxo-2,5-dihydro-furan-2-base oxygen base)-first-(E)-subunit]-3,3a, 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone P1(23mg, add successively in diastereo-isomerism liquid solution 0.077mmol) sodium hydride (3.5mg, 0.077mmol), methyl-iodide (1).This solution is stirred 2h and then at stirring at room 24h at 0 ° of C.With the segmentation between ethyl acetate and water of this solution, and with this water layer ethyl acetate extraction.With the salt water washing and concentrated of the organic layer of these merging.This resistates is carried out purifying by flash chromatography (carrying out wash-out with hexanaphthene-ethyl acetate (1/4)).This resistates is ground in pentane, to provide 1-methyl-(3aR*, 8bS*, 5 ' R*)-3-[1-(4-methyl-5-oxo-2,5-dihydro-furan-2-base oxygen base)-first-(E)-subunit]-3,3a, diastereomer (the white solid of 4,8b-tetrahydrochysene-1H-indeno [1,2-b] pyrroles-2-ketone P3,12mg, 49%).C 18H 17NO 4; MW:311.34; Mp130-135 ° of C; LCMS (method A) RT1.61min; ES312 (MH +), 353 (MH ++ MeCN); 1H NMR (400MHz, CDCl 3) δ 7.41 (1H, d), 7.19-7.35 (5H, m), 6.95 (1H, t), 6.15 (1H, s), 4.90 (1H, d), 3.83 (1H, m), 3.48 (1H, dd), 3.01 (3H, s), 2.98 (1H, dd), 2.02 (3H, s) ppm.
Table A: have the compound of chemical formula (I), the diastereomer that polarity is lower (R2=R3=R5=R7=R8=H, R6=Me, W=O)
Figure BDA00003342326200591
Figure BDA00003342326200601
Figure BDA00003342326200611
* with 1/1 mixture of the diastereomer of corresponding compd B.
Table B: have the compound of chemical formula (I), the diastereomer that polarity is higher (R2=R3=R5=R7=R8=H, R6=Me, W=O)
Figure BDA00003342326200613
Figure BDA00003342326200621
* with 1/1 mixture of the diastereomer of corresponding compd A.
The table C: have chemical formula (IIb) compound (R2=R3=R4=R5=R8=H, W=O)
Figure BDA00003342326200622
Figure BDA00003342326200631
The table D: have chemical formula (IIa) compound (W=O, R2=R3=R5=R8=H)
Figure BDA00003342326200633
The table E: have chemical formula (IV) compound (W=O, R1=Boc, R2=R3=R4=R5=H, R=Me)
Figure BDA00003342326200651
Figure BDA00003342326200652
The table F: have chemical formula (III) compound (R2=R3=R5=H, W=O)
Figure BDA00003342326200661
Figure BDA00003342326200662
Figure BDA00003342326200671
The table G: have chemical formula (IIIa) compound (R2=R3=R4=R5=H, W=O)
The table H: have chemical formula (VI) compound (R3=R4=R5=H, W=O)
Figure BDA00003342326200682
Figure BDA00003342326200683
Biological example
Glass fiber filter paper in culture dish (GFFP) has been assessed compound with chemical formula (I) to the influence of Sunflower Receptacle broomrape seed germination.Seed is carried out pre-treatment under moist and suitable temperature, to sprout stimulator in response to specific chemistry.
Test compound is dissolved in DMSO(10000mg l -1) in, and at room temperature it is stored in the moisture eliminator with siccative.Mother liquor is dissolved as suitable final experimental concentration with deionized water.
2006 (seed batch IN146) and 2008 (seed batch IN153), in (Seville, Manzanilla, Spain) (Manzanilla (Seville, Spain)) collects the seed of Sunflower Receptacle broomrape kind ' F ' from the Sunflower Receptacle land for growing field crops, and it is stored in room temperature.In order from heavy organic fragment, to separate this seed, use a kind of as by (Hartman(Hartmann) ﹠amp; Tanimonure(Ta Nimonu) (Plant Disease(" plant disease ") (1991), 75, p.494) the sucrose flotation technology of described improvement.Seed put in the separatory funnel and in water stir.When seed floats to the surface upward, discard the part of the water that comprises massive fragment.Seed is resuspended in the sucrose solution (1.20 proportions) of 2.5M and allows massive fragment sedimentation 60min.After removing fragment, with these seeds at 1% chlorine bleach liquor and 0.025%(v/v) polysorbas20 in the 2min that sterilizes.These seeds are poured on the two-layer cheese cloth, carry out rinsing and be resuspended in the aseptic deionized water with aseptic deionized water.Two milliliters the seed suspension that will comprise about 150-400 grain seed is coated on culture dish equably
Figure BDA00003342326200691
In two-layer aseptic glass fiber filter paper dish
Figure BDA00003342326200692
On.After with the aseptic deionized water of 3ml that these dishes are wetting, with culture dish with sealing film phonograph seal.Seed at 20 ° of C, was hatched 10 days in the dark, be used for seed and regulate.Drying is momently coiled on the upper strata that will have the seed of adjusting, is lined with in transferring in the culture dish of doing the GFFP dish, and wetting with the suitable testing liquid of 6ml.The compound that will have a chemical formula (I) is 0.001,0.01 and 0.1mg l -1Concentration test.Witchweed lactone analogue GR24(is commercially available as the mixture of isomers) included, as positive control and with 0.001% DMSO as negative control.All are carried out test processing repeats five times.Seed at 20 ° of C, is hatched in the dark again, and after 10 days sprouting checked.According to the Long(dragon) etc. people (Seed Science Research(" seed scientific research ") (2008), 18, p.125), in 5% acetic acid, with the radicle of the seed sprouted with blue ink (MIGROS(Migros company), Switzerland) dyeing 5min.After the dyeing, it is single anti-to use flat bed scanner (PULSTEK, OpticPro ST28) the scanning seed of the optical resolution with 1200dpi or use that digital SLR(is installed) camera support of camera (EOS5D of Canon (Canon)) takes.Assess the sprouting of 100 seeds of each repetition at digital image.When radicle is prominent when breaking in the seed coat, these seeds are considered as sprouting.Use SAS statistical package version 9.1 carries out variance analysis (GLM method) and sprouts the multiple comparisons (Sidak t-check) that data are handled mean value based on the per-cent of inverse sine conversion.The results are shown among the table 3-8 of the sprouting test of Orobanche seed.
These results illustrate, and compare with untreated contrast, and the compound of all tests has all shown the sprouting inductive effect.
Table 3: have the compound of chemical formula (I) to the influence of the Sunflower Receptacle broomrape seed germination of pretreated, seed batch IN146, kind F
* mean value; N=5x100 grain seed; Show data converted again
Mean value with same letter does not have significant difference, P≤0.05
Table 4: with the sprouting (%) of the compound with chemical formula (I) at the Sunflower Receptacle broomrape seed of the different concns processing, pretreated, batch IN146, kind F.
Figure BDA00003342326200702
Figure BDA00003342326200711
* with 1/1 mixture of the diastereomer of corresponding compd B.
#Mean value; N=5x100 grain seed; Show data converted again
Mean value with same letter does not have significant difference, P≤0.05
Mean value with letter ' e ' does not have significant difference with the water contrast (0.001%DMSO) that shows 0% sprouting.
Table 5: with the sprouting (%) of the compound with chemical formula (I) at the Sunflower Receptacle broomrape seed of the different concns processing, pretreated, batch IN146, kind F.
Figure BDA00003342326200712
* with 1/1 mixture of the diastereomer of corresponding compd B.
#Mean value; N=5x100 grain seed; Show data converted again
Mean value with same letter does not have significant difference, P≤0.05
Mean value with letter ' e ' does not have significant difference with the water contrast (0.001%DMSO) that shows 0% sprouting.
Table 6: with the sprouting (%) of the compound with chemical formula (I) at the Sunflower Receptacle broomrape seed of the different concns processing, pretreated, batch IN146, kind F.
Figure BDA00003342326200713
Figure BDA00003342326200721
#Mean value; N=5x100 grain seed; Show data converted again
Mean value with same letter does not have significant difference, P≤0.05
Mean value with letter ' e ' does not have significant difference with the water contrast (0.001%DMSO) that shows 0% sprouting.
Table 7: with the sprouting (%) of the compound with chemical formula (I) at the Sunflower Receptacle broomrape seed of the different concns processing, pretreated, batch IN153, kind F.
Figure BDA00003342326200722
* with 1/1 mixture of the diastereomer of corresponding compd B.
#Mean value; N=5x100 grain seed; Show data converted again
Mean value with same letter does not have significant difference, P≤0.05
Mean value with letter ' d ' does not have significant difference with the water contrast (0.001%DMSO) that shows 0% sprouting
Table 8: with the sprouting (%) of the compound with chemical formula (I) at the Sunflower Receptacle broomrape seed of the different concns processing, pretreated, batch IN153, kind F.
Figure BDA00003342326200723
Figure BDA00003342326200731
* with 1/1 mixture of the diastereomer of corresponding compd B.
#Mean value; N=5x100 grain seed; Show data converted again
Mean value with same letter does not have significant difference, P≤0.05
Mean value with letter ' g ' does not have significant difference with the water contrast (0.001%DMSO) that shows 0.3% sprouting

Claims (10)

1. compound with chemical formula (I)
Wherein
W is O or S;
R2 and R3 are hydrogen or C1-C3 alkyl independently;
R4 and R5 be independently hydrogen, halogen, nitro, cyano group, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxyl group, hydroxyl ,-OC (O) R9, amine, N-C1-C3 alkylamine or N, N-two-C1-C3 alkylamine;
R9 is hydrogen, C1-C6 alkyl, C1-C6 alkoxyl group or C1-C6 haloalkyl;
R6 and R7 are hydrogen, C1-C3 alkyl, hydroxyl or C1-C3 alkoxyl group independently;
R8 is hydrogen, nitro, cyano group, C1-C6 alkyl or C1-C6 haloalkyl;
R1 is hydrogen, C1-C6 alkoxyl group, hydroxyl, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine, by or can't help the C1-C6 alkyl that one to five R10 replaces, C1-C8 alkyl-carbonyl, C1-C8 alkoxy carbonyl, aryl, the aryl that is replaced by one to five R10, heteroaryl, the heteroaryl that is replaced by one to five R10, heterocyclic radical, the heterocyclic radical, the benzyl that are replaced by one to five R10 or the benzyl that is replaced by one to five R10;
R10 is hydrogen, cyano group, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxyl group, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;
A 1, A 2, A 3And A 4Be C-X or nitrogen independently of one another, wherein each X can be identical or different, and prerequisite is A 1, A 2, A 3And A 4In to be no more than two be nitrogen; And
X be hydrogen, halogen, cyano group, C1-C3 hydroxyalkyl ,-OC (O) R9, C1-C6 alkoxyl group, C1-C6 alkyl or C1-C6 haloalkyl, nitro, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine or NHC (O) R9;
Perhaps its salt or N-oxide compound.
2. a kind of compound according to claim 1, wherein W is O.
3. a kind of compound according to claim 2, wherein
R2 and R3 are hydrogen, methyl or ethyl independently;
R4 and R5 are hydrogen, hydroxyl, methyl or ethyl independently;
R6, R7 and R8 are hydrogen, methyl or ethyl independently;
R1 is hydrogen, the C1-C6 alkoxyl group, by or the heterocyclic radical of can't help C1-C6 alkyl that one to five R10 replaces, C1-C8 alkyl-carbonyl, C1-C8 alkoxy carbonyl, aryl, the aryl that is replaced by one to five R10, heteroaryl, the heteroaryl that is replaced by one to five R10, heterocyclic radical, being replaced by one to five R10, benzyl or the benzyl that is replaced by one to five R10;
R10 is hydrogen, cyano group, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxyl group or C1-C6 haloalkyl independently;
A 1, A 2, A 3And A 4Be C-X independently of one another; And
X is hydrogen, hydroxyl, halogen, cyano group, methyl, ethyl, n-propyl, methylol, trifluoromethyl or methoxyl group.
4. a plant growth regulators or seed germination promote composition, comprise a kind of according to each described compound in the aforesaid claim, and acceptable preparation adjuvant on a kind of agricultural.
5. method that is used for a place coordinate plant growth, wherein this method comprises composition according to claim 4 from a kind of plant growth regulating amount to this place that use.
6. method that be used for to promote seed germination comprises to these seeds or a place comprising seed and uses a kind of composition according to claim 4 that promotes the seed germination amount.
7. one kind is used for the control method for weed, comprises to a place that comprises weed seed and uses a kind of composition according to claim 4 that promotes the seed germination amount, allowing these seed germinations, and uses a kind of herbicide after seedling to this place then.
8. method for the manufacture of the compound with chemical formula (I)
Figure FDA00003342326100031
May further comprise the steps:
A) handle a kind of compound with chemical formula (VI) with a kind of sulfonamide derivatives, reduce to provide a kind of compound with chemical formula (III) subsequently;
Figure FDA00003342326100041
B) under alkaline condition, handle this compound with chemical formula (III) to form a kind of compound with chemical formula (II) with a kind of carbamate derivatives; And
Figure FDA00003342326100042
C) under alkaline condition, handle the compound that this has chemical formula (II) with a kind of 5H-furanone derivatives;
Figure FDA00003342326100043
Figure FDA00003342326100044
Wherein W is O or S; R2 and R3 are hydrogen or C1-C3 alkyl independently; R4 and R5 be independently hydrogen, halogen, nitro, cyano group, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxyl group, hydroxyl ,-OC (O) R9, amine, N-C1-C3 alkylamine or N, N-two-C1-C3 alkylamine; R9 is hydrogen, C1-C6 alkyl, C1-C6 alkoxyl group or C1-C6 haloalkyl; R6 and R7 are hydrogen, C1-C3 alkyl, hydroxyl or C1-C3 alkoxyl group independently; R8 is hydrogen, nitro, cyano group, C1-C6 alkyl or C1-C6 haloalkyl; R1 is hydrogen, C1-C6 alkoxyl group, hydroxyl, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine, by or can't help the C1-C6 alkyl that one to five R10 replaces, C1-C8 alkyl-carbonyl, C1-C8 alkoxy carbonyl, aryl, the aryl that is replaced by one to five R10, heteroaryl, the heteroaryl that is replaced by one to five R10, heterocyclic radical, the heterocyclic radical, the benzyl that are replaced by one to five R10 or the benzyl that is replaced by one to five R10; R10 is hydrogen, cyano group, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxyl group, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl; A 1, A 2, A 3And A 4Be C-X or nitrogen independently of one another, wherein each X can be identical or different, and prerequisite is A 1, A 2, A 3And A 4In to be no more than two be nitrogen; And X be hydrogen, halogen, cyano group, C1-C3 hydroxyalkyl ,-OC (O) R9, C1-C6 alkoxyl group, C1-C6 alkyl or C1-C6 haloalkyl, nitro, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine or NHC (O) R9.
9. compound with chemical formula (II)
Figure FDA00003342326100051
Wherein
W is O or S;
R2 and R3 are hydrogen or C1-C3 alkyl independently;
R4 and R5 be independently hydrogen, halogen, nitro, cyano group, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxyl group, hydroxyl ,-OC (O) R9, amine, N-C1-C3 alkylamine or N, N-two-C1-C3 alkylamine;
R9 is hydrogen, C1-C6 alkyl, C1-C6 alkoxyl group or C1-C6 haloalkyl;
R8 is hydrogen, nitro, cyano group, C1-C6 alkyl or C1-C6 haloalkyl;
R1 is hydrogen, C1-C6 alkoxyl group, hydroxyl, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine, by or can't help the C1-C6 alkyl that one to five R10 replaces, C1-C8 alkyl-carbonyl, C1-C8 alkoxy carbonyl, aryl, the aryl that is replaced by one to five R10, heteroaryl, the heteroaryl that is replaced by one to five R10, heterocyclic radical, the heterocyclic radical, the benzyl that are replaced by one to five R10 or the benzyl that is replaced by one to five R10;
R10 is hydrogen, cyano group, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxyl group, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl;
A 1, A 2, A 3And A 4Be C-X or nitrogen independently of one another, wherein each X can be identical or different, and prerequisite is A 1, A 2, A 3And A 4In to be no more than two be nitrogen; And
X be hydrogen, halogen, cyano group, C1-C3 hydroxyalkyl ,-OC (O) R9, C1-C6 alkoxyl group, C1-C6 alkyl or C1-C6 haloalkyl, nitro, amine, N-C1-C6 alkylamine, N, N-two-C1-C6 alkylamine or NHC (O) R9;
Perhaps its salt or N-oxide compound.
10. has the compound of chemical formula (I) as the purposes of a plant growth regulators or a kind of seed germination promotor.
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GB2535911B (en) 2013-10-25 2020-10-21 Sound Agriculture Company Strigolactone formulations and uses thereof
GB201403334D0 (en) 2014-02-26 2014-04-09 Syngenta Participations Ag Plant growth regulating compounds
JP6948264B2 (en) 2015-04-24 2021-10-13 サウンド アグリカルチャー カンパニー Methods for improving crop water flow
US11192886B2 (en) * 2016-07-22 2021-12-07 Medshine Discovery Inc. S1P1 agonist and application thereof
GB201615544D0 (en) * 2016-09-13 2016-10-26 Syngenta Participations Ag Plant Growth regulator compounds
GB201702158D0 (en) 2017-02-09 2017-03-29 Syngenta Participations Ag Germination promoters
GB201912595D0 (en) 2019-09-02 2019-10-16 Syngenta Crop Protection Ag Plant growth regulator compounds
GB202013756D0 (en) 2020-09-02 2020-10-14 Syngenta Crop Protection Ag Plant growth regulator compounds

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1311788A (en) * 1998-08-03 2001-09-05 应用研究***Ars股份公司 Process for the synthesis of (1H)-benzo [C] quinolizin-3-ones derivatives
WO2009138655A2 (en) * 2008-04-23 2009-11-19 Institut National De La Recherche Agronomique Method for treating a higher plant with a view to controlling the growth and architecture thereof
WO2010066780A1 (en) * 2008-12-12 2010-06-17 Syngenta Participations Ag Spiroheterocyclic n-oxypiperidines as pesticides

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5946269A (en) 1982-09-08 1984-03-15 Yoshitomi Pharmaceut Ind Ltd Indeno(1,2-b)pyrrole derivative
BR8600161A (en) 1985-01-18 1986-09-23 Plant Genetic Systems Nv CHEMICAL GENE, HYBRID, INTERMEDIATE PLASMIDIO VECTORS, PROCESS TO CONTROL INSECTS IN AGRICULTURE OR HORTICULTURE, INSECTICIDE COMPOSITION, PROCESS TO TRANSFORM PLANT CELLS TO EXPRESS A PLANTINIDE TOXIN, PRODUCED BY CULTURES, UNITED BY BACILLA
EP0374753A3 (en) 1988-12-19 1991-05-29 American Cyanamid Company Insecticidal toxines, genes coding therefor, antibodies binding them, transgenic plant cells and plants expressing these toxines
DK0427529T3 (en) 1989-11-07 1995-06-26 Pioneer Hi Bred Int Larval killing lactins and plant insect resistance based thereon
UA48104C2 (en) 1991-10-04 2002-08-15 Новартіс Аг Dna fragment including sequence that codes an insecticide protein with optimization for corn, dna fragment providing directed preferable for the stem core expression of the structural gene of the plant related to it, dna fragment providing specific for the pollen expression of related to it structural gene in the plant, recombinant dna molecule, method for obtaining a coding sequence of the insecticide protein optimized for corn, method of corn plants protection at least against one pest insect
US5530195A (en) 1994-06-10 1996-06-25 Ciba-Geigy Corporation Bacillus thuringiensis gene encoding a toxin active against insects
AU2002214158B2 (en) 2000-12-07 2007-01-18 Syngenta Limited Plant derived hydroxy phenyl pyruvate dioxygenases (HPPD) resistant against triketone herbicides and transgenic plants containing these dioxygenases
JP2003055366A (en) * 2001-08-20 2003-02-26 Shiseido Co Ltd Lactone derivative, plant growth regulator and rooting inductor containing the same as active ingredient
AU2002361696A1 (en) 2001-12-17 2003-06-30 Syngenta Participations Ag Novel corn event
FR2865897B1 (en) 2004-02-10 2006-06-09 Univ Toulouse MODULATORS FOR THE DEVELOPMENT OF MYCORRHIZIAN FUNGI WITH ARBUSCLES, AND.
WO2005097093A1 (en) 2004-04-01 2005-10-20 Neurocrine Biosciences, Inc. Sleep inducing compounds and methods relating thereto
EP1859044B1 (en) 2005-03-18 2014-07-02 Wageningen Universiteit Resistance against parasitic weeds
TW200904331A (en) * 2007-06-15 2009-02-01 Bayer Cropscience Sa Pesticidal composition comprising a strigolactone derivative and an insecticide compound
WO2010125065A2 (en) 2009-04-28 2010-11-04 Bayer Cropscience Ag Compositions comprising a strigolactone compound and a chito-oligosaccharide compound for enhanced plant growth and yield
WO2010137662A1 (en) 2009-05-27 2010-12-02 独立行政法人理化学研究所 Plant branching inhibitor, method for producing same, and plant branching inhibitory composition

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1311788A (en) * 1998-08-03 2001-09-05 应用研究***Ars股份公司 Process for the synthesis of (1H)-benzo [C] quinolizin-3-ones derivatives
WO2009138655A2 (en) * 2008-04-23 2009-11-19 Institut National De La Recherche Agronomique Method for treating a higher plant with a view to controlling the growth and architecture thereof
WO2010066780A1 (en) * 2008-12-12 2010-06-17 Syngenta Participations Ag Spiroheterocyclic n-oxypiperidines as pesticides

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ALAN W. JOHNSON等: "The preparation of synthetic analogues of strigol", 《JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104363759A (en) * 2012-06-11 2015-02-18 先正达参股股份有限公司 Robot system
CN107683280A (en) * 2015-06-03 2018-02-09 先正达参股股份有限公司 plant growth regulating compound
CN111867378A (en) * 2018-03-16 2020-10-30 先正达参股股份有限公司 Plant growth regulating compounds
CN111886232A (en) * 2018-03-16 2020-11-03 先正达参股股份有限公司 Plant growth regulator compounds

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